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V SIMPOSIO del CONSEJO de HEMODINAMIA SAC 2015
Mas alla de las Fronteras del Intervencionismo Cardiovascular
ACCESO en el STEMI RADIAL vs FEMORAL Dr Cesar Pardinas Montevideo Uruguay
LA VIA TRANSRADIAL DEBERIA SER EL ACCESO DE ELECCION o ldquo DEFAULTrdquo PARA LOS PACIENTES CON SCA TRATADOS CON INTERVENCIONISMO PERCUTANEO
Cine frame from the first selective coronary arteriogram recorded by F Mason Sones Jr on
October 30 1958
Cheng T O Circulation 2003107e42
Copyright copy American Heart Association Inc All rights reserved
EDUCATIONAL CONTENT ENDORSED BY EAPCI A REGISTERED BRANCH
OF THE EUROPEAN SOCIETY OF CARDIOLOGY
Figure 1
copy 2
014 E
uro
pa D
igital amp
Publis
hin
g A
ll rig
hts
reserv
ed
The PCR-EAPCI Textbook ndash Percutaneous interventional cardiovascular medicine
Vascular access Olivier Bertrand Rodney de Palma David Meerkin
EDUCATIONAL CONTENT ENDORSED BY EAPCI A REGISTERED BRANCH
OF THE EUROPEAN SOCIETY OF CARDIOLOGY
Figure 6
copy 2
014 E
uro
pa D
igital amp
Publis
hin
g A
ll rig
hts
reserv
ed
The PCR-EAPCI Textbook ndash Percutaneous interventional cardiovascular medicine
Vascular access Olivier Bertrand Rodney de Palma David Meerkin
Procedimientos INCC 2014
N 1455
Acceso radial en el tratamiento intervencionista del infarto agudo de miocardio con sobreelevacioacuten del ST Dr Gabriel Pintos INCC
OBJETIVO Evaluar los resultados obtenidos en el tratamiento intervencionista de pacientes con IAMcST realizado por acceso radial
MEacuteTODO Estudio analiacutetico de cohorte
Desde el 01012003 hasta el 31122009 se trataron 2114 pacientes con IAMcST en curso (lt24 hs de evolucioacuten) Se incluyeron en la base de datos de la institucioacuten y se registroacute prospectivamente
bull Comorbilidad bull Procedimiento realizado bull Tipo y nuacutemero de arterias tratadas bull Dispositivos utilizados bull Evolucioacuten pos procedimiento inmediata
0
20
40
60
80
100
393 874 96
n꞊280 n꞊657 n꞊1177
Incidencia del acceso radial en IAMcST seguacuten eacutepoca
SUPERVIVENCIA SEGUacuteN ACCESO VASCULAR
p lt 001
diacuteas
AF 057
AR 068
CONCLUSIONES
El ACCESO RADIAL se asocioacute a disminucioacuten del riesgo de
MUERTE a corto y largo plazo en el tratamiento intervencionista
del IAMcST y por tanto PODRIA SER LA VIA DE ABORDAJE DE
ELECCION EN ESTOS PACIENTES
Adoption of Radial Access in PCI in US Trend in the Use of r-PCI Over Time in the Overall amp Key Subgroups
Feldman et al Circulation 20131272295
All Patients
Pts with Stable angina NSTE ACS STEMI
Overall Radial PCI
R
ad
ial
20
07
- Q
tr
20
07
- Q
tr
20
08
- Q
tr
20
08
- Q
tr
20
09
- Q
tr
20
09
- Q
tr
20
10
- Q
tr
20
10
- Q
tr
20
11
- Q
tr
20
11
- Q
tr
20
12
- Q
tr
20
12
- Q
tr
20
18
16
14
12
10
8
6
4
2
161
R
ad
ial
20
07
- Q
tr
20
07
- Q
tr
20
08
- Q
tr
20
08
- Q
tr
20
09
- Q
tr
20
09
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tr
20
10
- Q
tr
20
10
- Q
tr
20
11
- Q
tr
20
11
- Q
tr
20
12
- Q
tr
20
12
- Q
tr
Male Female 20
18
16
14
12
10
8
6
4
2
R
ad
ial
20
07
- Q
tr
20
07
- Q
tr
20
08
- Q
tr
20
08
- Q
tr
20
09
- Q
tr
20
09
- Q
tr
20
10
- Q
tr
20
10
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tr
20
11
- Q
tr
20
11
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tr
20
12
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tr
20
12
- Q
tr
UANSTEMI STEMI Stable Angina 2
0
1
8
1
6
1
4
1
2
1
0
8
6
4
2
IAM
bull All antithrombotic agents (except fondaparinux bivalirudin) are associated with increased bleeding risk
bull Aspirin and heparin reduce death MI at 30 days in NSTE-ACS
Choice of arterial access site and outcomes in patients with acute coronary
siacutendromes managed with an early invasive strategy the ACUITY trial Hamon M Rasmussen LH Manoukian SV Cequier A Lincoff MA Rupprecht HJ Gersh BJ Mann T Bertrand ME Mehran R Stone GW
AIMS The purpose of this study was to evaluate the impact of arterial access site on bleeding and ischaemic outcomes overall and by
treatment strategy in patients with acute coronary syndromes (ACS)
METHODS AND RESULTS In the ACUITY trial 13819 patients with moderate and high-risk ACS were randomised to either heparin
(unfractionated or enoxaparin) plus a glycoprotein IIbIIIa inhibitor (GPI) bivalirudin plus a GPI or bivalirudin alone
Per operator choice femoral access was utilised in 11989 patients (938) and radial Access in 798 patients (62) There was no significant
difference in composite ischaemia between the radial and femoral approaches at 30 days (81 vs 75 p=018) or 1 year (147 vs
155 p=077)although fewer major bleeding complications occurred with the use of radial access (30vs48 p=003) Use of
bivalirudin monotherapy was associated with significantly less 30-day major bleeding than heparin plus GPI after femoral access
(30 vs 58 plt00001) but not with radial access (42 vs 22 P=019)
Major or minor organ bleeding was reduced with bivalirudin monotherapy compared to heparin plus GPI to a similar extent with both
femoral (41 vs 74 Plt00001) and radial (49 vs 72 P=026) access
EuroIntervention 2009 May5(1)115-20
CONCLUSIONS
Transradial compared to femoral arterial access is associated with similar rates of composite ischaemia
anwith fewer major bleeding complications in patients with ACS managed invasively
Bivalirudin monotherapy compared to heparin plus GPIs significantly reduces
access site related major bleeding complications with femoral
but not radial artery access though non-access site related bleeding is reduced by
bivalirudin monotherapy in all patients
0 5 10 15 20 25 30
0
20
40
60
80
100
120
140
Mo
rta
lity
(
)
CURE=Clopidogrel in Unstable angina to prevent Recurrent ischemic Events (study) OASIS=Organization to Assess
Strategies for Ischemic Syndromes (study)
Reproduced with permission from Eikelboom JW et al Circulation 2006114774-782
Major Bleeding During First 30 Days Is Associated With Mortality Meta-analysis of 34146
ACS patients from the randomized OASIS OASIS-2 and CURE trials assessed the
association between bleeding within the first 30 days and death
Without major bleeding
With major bleeding
Days
Mo
rtality
(
)
Days from randomization
0 30 60 90 120 150 180 210 240 270 300 330 360 390
0
5
15
30
10
25
20
Major bleed only (without MI) (n=551)
Both MI and major bleed (n=94)
No MI or major bleed (n=12557)
MI only (without major bleed) (n=611)
Data on file The Medicines Company Parsippany NJ
289
125
86
34
Univariate analysis of 13819 patients from ACUITY
Impact of Non-CABG Major Bleeding and
MI at 30 Days on 1-Year Mortality
Radial Access 798 pts 62
Am Heart J 2009 Jan157(1)164-9 Epub 2008 Nov 6
Am Heart J 2009 Jan157(1)164-9 Epub 2008 Nov 6
Hypothetical mechanisms linking bleeding and mortality
Steg P G et al Eur Heart J 2011321854-
1864
Existing bleeding scores
bull TIMI Laboratory-based (hemoglobin hematocrit decrease)
bull GUSTO Clinical (severity)-based
bull GRACE Simplified laboratory and clinical
bull CURE Major minor (combined clin + lab)
bull ACUITY Major (intracranial-ocular access-site retroperit) lab
bull REPLACE-2 bull ISAR-REACT 3 bull PLATO bull STEEPLE bull CURRENT-OASIS
Thrombolysis conservative
PCI-based
BARC (Bleeding Academic Research Consortium) definitions
Mehran et al Circulation 20111232736-2747
bull Type 0 no evidence of bleeding bull Type 1 bleeding that is not actionable without
need for hospitalization or treatment (eg bruising hematoma nosebleeds etc)
bull Type 2 any clinically overt sign of hemorrhage that is actionable but does not meet criteria for type 3 4 or 5 Must meet at least 1 of following criteria ndash Requires intervention ndash Leads to hospitalization MANEJO MEDICO ndash Prompts evaluation
BARC (Bleeding Academic Research Consortium) definitions
Mehran et al Circulation 20111232736-2747
bull Type 3 clinical laboratory andor imaging evidence of bleeding with healthcare provider responses ndash BARC type 3a
bull any transfusion with overt bleeding bull overt bleeding plus hemoglobin drop ge3 to lt5 gdL
ndash BARC type 3b bull overt bleeding plus hemoglobin drop gt5 gdL bull Cardiac tamponade bull Bleeding requiring surgical intervention for control (excluding dentalnasalskinhemorrhoid) bull Bleeding requiring intravenous vasoactive drugs
ndash BARC type 3c bull Intracranial hemorrhage subcategories confirmed by autopsy
imaging or lumbar puncture bull Intraocular bleed compromising vision
BARC Bleeding Academic Research Consortium) definitions
Mehran et al Circulation 20111232736-2747
bull Type 4 Coronary Artery Bypass Graftndashrelated bleeding ndash Perioperative intracranial bleeding within 48 hours ndash Reoperation after closure of sternotomy for the purpose of controlling bleeding ndash Transfusion of ge5 U whole blood or packed red blood cells within a 48-hour period ndash Chest tube output 2 L within a 24-hour period
bull Type 5 ndash fatal bleeding bull Probable fatal bleeding (type 5a)
ndash bleeding that is clinically suspicious as the cause of death but the bleeding is not directly observed and there is no autopsy or confirmatory imaging
bull Definite fatal bleeding (type 5b) ndash bleeding that is directly observed (by either clinical specimen [blood
emesis stool etc] or imaging) or confirmed on autopsy
26 VCD
11
NSTEACS or STEMI with invasive management Aspirin+P2Y12 blocker
Trans-Femoral Access
Trans-Radial Access
To demonstrate that trans-radial intervention as
compared to femoral access site is associated to lower
rate of the composite endpoint of Death MI or Stroke
within the first 30 days
1deg co-Primary Objective
6 vs 42 βlt10 α 25 8200 patients
Adaptive study Design sample size (SS) will be increased
by the cross-over rate at 70 of planned SS
MATRIX Access site NCT01433627
MATRIX Access
39 93 132 200 276 380 490 685 857 1002 1190
1400 1684 1972 2248
2584 2926
3256 3560
3875 4144
4452 4726
5000 5322
5655 5896 6184
6458 6742 6982 7235 7444 7638 7844 8073
8404
Cumulative enrollment by month
8404
8404
8404 patients with ACS undergoing coronary angiography plusmn PCI from 11th Oct 2011 to 7th Nov 2014
Operator Eligibility Criteria Interventional cardiologist expertise in TRI and TFI including at least 75 transradial coronary interventions and at least 50 of interventions performed via radial route in the year preceding site initiation
Complete follow-up to 30 days available in 4183 (997) of radial and 4191 (99middot6) of femoral cohorts
Am Heart J 2014 Dec168(6)838-45e6
Cross Over and Procedural Success Rates
941 of radial and 974 of femoral cohorts received respective treatment as allocated
In 58 of radial and 23 of TF cohort the allocated access was attempted but failed
In 3 (01) in the radial and 13 (03) patients in the femoral groups the allocated access was not attempted
P=077 Plt0001
TIMI lt3 andor final stenosis gt30
88
103
15 significant reduction at nominal 5 alpha
which is however NOT significant at the pre-specificed
alpha of 25
Primary EP MACE
Femoral
Radial
Rate Ratio 083 95 CI 073 to 096 p=00092
117
98
NNTB 53 Femoral
Radial
Primary EP NACE
Mortalidad Total
IAM
Fatal and ST EPs All-Cause Cardiac non-CV mortality type of stent thrombosis
RR072
(053-099)
P=0045
RR 075
(054-104)
P=008 1
13
06
1
0
02
04
06
08
1
12
14
Radial Femoral
P=069
P=066
Mortality Stent Thrombosis
NNTB 167
Bleeding endpoints BARC TIMI GUSTO access vs non-access related
14
25
P=0013
RR 067 049-092
P=00004
RR 037 021-066
BARC 3 or 5
P=00098
RR 064 045-090
P=008
RR 072 050-104 P=020
RR 078 053-114
Major
or minor
moderate
or severe
P=082
P=068
Rardial Better Femoral Better 1
HAZARD RATIO (95 CI)
P-VALUES
Superiority Interaction
089 Intermediate (548-991)
075 (060-094)
104 (082-132) 076 0011
Centrersquos annual
volume of PCI
Low (247-544)
Intermediate (654-790)
Centrersquos
Proportion of
radial PCI
Low (149-644)
NSTE-ACS (tpndash) ACS type
STEMI
lt75 Age
ge75 023 088 (070-109)
082 (068-097) 0023 062
NACE Subgroup Analysis
High (1000-1950)
High (800-980)
NSTE-ACS (tp+)
Men Sex
Women
lt25 BMI
ge25
No
Ticagrelor or
prasugrel Yes
No Diabetes
Yes
lt60 GFR
ge60
No
History of
PVD Yes
2 025 050
075 (058-097) 0025
00048
101 (079-129)
095 (075 -122) 071
095
064 (051-080) lt0001
044
086 (068-108)
058 (033-103) 0059
019
085 (071-102) 007
0012 072 (056-093)
089 (076-105) 016 018
009 086 (073-102)
079 (063-099) 0038 053
007 083 (068-102)
084 (070-101) 006 094
045 091 (071-117)
080 (068-094) 008 043
001 078 (065-094)
086 (070-107) 018 051
060 091 (064-130)
083 (071-096) 0012 064
Radial Better Femoral Better 1
HAZARD RATIO (95 CI)
P-VALUES
Superiority Interaction
Intermediate (654-790)
Centrersquos
Proportion
of radial PCI
Low (149-644)
NSTE-ACS (tpndash) ACS
type
STEMI
Subgroup Analysis
High (800-980)
NSTE-ACS (tp+)
2
00157
128 (071-232)
069 (040 -119) 018
041
048 (028-081) 0006
010
087 (059-129) 049
049 (028-087) 0012
Intermediate (654-790) Centrersquos
Proportion
of radial PCI
Low (149-644)
NSTE-ACS (tpndash) ACS
type
STEMI
High (800-980)
NSTE-ACS (tp+)
020
090 (054-150)
057 (031 -103) 006
068
056 (032-097) 0035
054
062 (041-094)
166 (028-100) 058
0022
070 (042-117) 017
Mortality
Bleeding
4 050 025
1 2 050 025
Updated Meta-analysis 19328 ACS patients being randomly allocated to radial or femoral access
Rardial Better Femoral Better 1 4 025 050 2
Pre-Rival RIVAL Post-RIVAL MATRI
X Combined
Non-CABG
major bleeds
Death
myocardial
infarction or
stroke
Death
Myocardial
Infarction
Stroke
Pre-Rival RIVAL Post-RIVAL MATRI
X Combined
Pre-Rival RIVAL Post-RIVAL MATRI
X Combined
Pre-Rival RIVAL Post-RIVAL MATRI
X Combined
Pre-Rival RIVAL Post-RIVAL MATRI
X Combined
SUBGROUP Risk Ratio (95CI) P Value
Heterogenity
P Value I2
073 (043-123) 039 (023-067)
058 (046-072)
041 (022-076)
lt00001 0 05
1
067 (048-093) 086 (076-098) 086 (077-095)
098 (076-127)
00051 0 09
7
058 (039-087) 073 (053-099) 072 (060-088) 00011 0 10
0
085 (039-190) 091 (078-106) 091 (079-104)
092 (065-131)
01
6 0 08
8
068 (049-092)
082 (052-129)
077 (046-128) 086 (058-129)
073 (012-447)
140 (045-440) 100 (050-200) 105 (069-160)
143 (072-283)
08
0 0 07
5
026 (006-123)
Summary bull Among patients with an ACS with or without ST-segment
elevation who underwent invasive management the use
of radial access for coronary angiography plusmn PCI reduced
the rate of net adverse clinical events with a number
needed to treat for benefit of 53
ndash Differences between groups were driven by reductions in BARC
major bleeding unrelated to CABG and all-cause mortality with
radial access
bull Our results in conjunction with the updated meta-
analysis suggest that radial approach should
become the default access for patients with
ACS undergoing invasive management
Radial Acces 61000 menos Muertes
LA VIA TRANSRADIAL DEBERIA SER EL ACCESO DE ELECCION o ldquo DEFAULTrdquo PARA LOS PACIENTES CON SCA TRATADOS CON INTERVENCIONISMO PERCUTANEO
LA VIA TRANSRADIAL DEBERIA SER EL ACCESO DE ELECCION PARA TODO PACIENTE CONSIN SCA TRATADOS CON INTERVENCIONISMO PERCUTANEO
GRACIAS POR SU ATENCION
MACE
Mortality
No interaction between access and anticoagulant use in a post- hoc analysis of the subgroup of 7213 patients randomized to bivalirudin or unfractionated heparin for the two co-primary outcomes all-cause mortality or BARC 3 or 5 bleeding
Relevance of bleeding as a clinical endpoint
bull Availability of potent antithrombotic therapy including ndash ASA ndash P2Y12 inhibitors (clopidogrel prasugrel ticagrelor) ndash heparin ndash GP IIbIIIa inhibitors ndash direct thrombin inhibitors
bull has led to a reduction in ischemic events bull but is associated with an increased risk of
bleeding bull the increase in bleeding is associated with worse
clinical outcome
Rationale for a new bleeding definition
bull Increased importance of bleeding as prognostic factor
bull Need for assessment of bleeding in RCTs and registries
bull Lack of comparability bull Need for standardized definitions to avoid
erroneous conclusions
ndash regarding safety of a given agent ndash regarding superiority of one agent over another
Open questions regarding BARC
bull Why 48-hour window for CABG-related bleeding
bull Why type 1 bdquonot actionableldquo when patient may bdquotake actionldquo such as discontinuing medication (with potentially serious consequences such as ST)
bull Why consider intraocular bleed equivalent to intracranial bleed for BARC 3c
bull Type 1 bleed subject to misinterpretation by the patient
Hicks et al (editorial) Circulation 20111232664
Conclusion
bull BARC is a new objective hierarchically graded classification of bleeding
(Mehran Circulation [June 14] 20111232736)
bull BARC is based on consensus rather than data-driven
bull Prospective validation is warranted ndash across the spectrum of IHD
ndash across management strategies (conservative invasive)
ndash in the context of all invasive procedures (PCI CABG endovascular TAVI)
Conclusion (2)
bull Final validation of BARC and proof of its utility depend on
ndash its use by all future RCTs as common safety endpoint
ndash unanimous assessment procedure (questionnaires)
bull More important than using one or the other bleeding risk score is the agreement and commitment among clinical trialists to use the same score for comparability of data
LA VIA TRANSRADIAL DEBERIA SER EL ACCESO DE ELECCION o ldquo DEFAULTrdquo PARA LOS PACIENTES CON SCA TRATADOS CON INTERVENCIONISMO PERCUTANEO
Cine frame from the first selective coronary arteriogram recorded by F Mason Sones Jr on
October 30 1958
Cheng T O Circulation 2003107e42
Copyright copy American Heart Association Inc All rights reserved
EDUCATIONAL CONTENT ENDORSED BY EAPCI A REGISTERED BRANCH
OF THE EUROPEAN SOCIETY OF CARDIOLOGY
Figure 1
copy 2
014 E
uro
pa D
igital amp
Publis
hin
g A
ll rig
hts
reserv
ed
The PCR-EAPCI Textbook ndash Percutaneous interventional cardiovascular medicine
Vascular access Olivier Bertrand Rodney de Palma David Meerkin
EDUCATIONAL CONTENT ENDORSED BY EAPCI A REGISTERED BRANCH
OF THE EUROPEAN SOCIETY OF CARDIOLOGY
Figure 6
copy 2
014 E
uro
pa D
igital amp
Publis
hin
g A
ll rig
hts
reserv
ed
The PCR-EAPCI Textbook ndash Percutaneous interventional cardiovascular medicine
Vascular access Olivier Bertrand Rodney de Palma David Meerkin
Procedimientos INCC 2014
N 1455
Acceso radial en el tratamiento intervencionista del infarto agudo de miocardio con sobreelevacioacuten del ST Dr Gabriel Pintos INCC
OBJETIVO Evaluar los resultados obtenidos en el tratamiento intervencionista de pacientes con IAMcST realizado por acceso radial
MEacuteTODO Estudio analiacutetico de cohorte
Desde el 01012003 hasta el 31122009 se trataron 2114 pacientes con IAMcST en curso (lt24 hs de evolucioacuten) Se incluyeron en la base de datos de la institucioacuten y se registroacute prospectivamente
bull Comorbilidad bull Procedimiento realizado bull Tipo y nuacutemero de arterias tratadas bull Dispositivos utilizados bull Evolucioacuten pos procedimiento inmediata
0
20
40
60
80
100
393 874 96
n꞊280 n꞊657 n꞊1177
Incidencia del acceso radial en IAMcST seguacuten eacutepoca
SUPERVIVENCIA SEGUacuteN ACCESO VASCULAR
p lt 001
diacuteas
AF 057
AR 068
CONCLUSIONES
El ACCESO RADIAL se asocioacute a disminucioacuten del riesgo de
MUERTE a corto y largo plazo en el tratamiento intervencionista
del IAMcST y por tanto PODRIA SER LA VIA DE ABORDAJE DE
ELECCION EN ESTOS PACIENTES
Adoption of Radial Access in PCI in US Trend in the Use of r-PCI Over Time in the Overall amp Key Subgroups
Feldman et al Circulation 20131272295
All Patients
Pts with Stable angina NSTE ACS STEMI
Overall Radial PCI
R
ad
ial
20
07
- Q
tr
20
07
- Q
tr
20
08
- Q
tr
20
08
- Q
tr
20
09
- Q
tr
20
09
- Q
tr
20
10
- Q
tr
20
10
- Q
tr
20
11
- Q
tr
20
11
- Q
tr
20
12
- Q
tr
20
12
- Q
tr
20
18
16
14
12
10
8
6
4
2
161
R
ad
ial
20
07
- Q
tr
20
07
- Q
tr
20
08
- Q
tr
20
08
- Q
tr
20
09
- Q
tr
20
09
- Q
tr
20
10
- Q
tr
20
10
- Q
tr
20
11
- Q
tr
20
11
- Q
tr
20
12
- Q
tr
20
12
- Q
tr
Male Female 20
18
16
14
12
10
8
6
4
2
R
ad
ial
20
07
- Q
tr
20
07
- Q
tr
20
08
- Q
tr
20
08
- Q
tr
20
09
- Q
tr
20
09
- Q
tr
20
10
- Q
tr
20
10
- Q
tr
20
11
- Q
tr
20
11
- Q
tr
20
12
- Q
tr
20
12
- Q
tr
UANSTEMI STEMI Stable Angina 2
0
1
8
1
6
1
4
1
2
1
0
8
6
4
2
IAM
bull All antithrombotic agents (except fondaparinux bivalirudin) are associated with increased bleeding risk
bull Aspirin and heparin reduce death MI at 30 days in NSTE-ACS
Choice of arterial access site and outcomes in patients with acute coronary
siacutendromes managed with an early invasive strategy the ACUITY trial Hamon M Rasmussen LH Manoukian SV Cequier A Lincoff MA Rupprecht HJ Gersh BJ Mann T Bertrand ME Mehran R Stone GW
AIMS The purpose of this study was to evaluate the impact of arterial access site on bleeding and ischaemic outcomes overall and by
treatment strategy in patients with acute coronary syndromes (ACS)
METHODS AND RESULTS In the ACUITY trial 13819 patients with moderate and high-risk ACS were randomised to either heparin
(unfractionated or enoxaparin) plus a glycoprotein IIbIIIa inhibitor (GPI) bivalirudin plus a GPI or bivalirudin alone
Per operator choice femoral access was utilised in 11989 patients (938) and radial Access in 798 patients (62) There was no significant
difference in composite ischaemia between the radial and femoral approaches at 30 days (81 vs 75 p=018) or 1 year (147 vs
155 p=077)although fewer major bleeding complications occurred with the use of radial access (30vs48 p=003) Use of
bivalirudin monotherapy was associated with significantly less 30-day major bleeding than heparin plus GPI after femoral access
(30 vs 58 plt00001) but not with radial access (42 vs 22 P=019)
Major or minor organ bleeding was reduced with bivalirudin monotherapy compared to heparin plus GPI to a similar extent with both
femoral (41 vs 74 Plt00001) and radial (49 vs 72 P=026) access
EuroIntervention 2009 May5(1)115-20
CONCLUSIONS
Transradial compared to femoral arterial access is associated with similar rates of composite ischaemia
anwith fewer major bleeding complications in patients with ACS managed invasively
Bivalirudin monotherapy compared to heparin plus GPIs significantly reduces
access site related major bleeding complications with femoral
but not radial artery access though non-access site related bleeding is reduced by
bivalirudin monotherapy in all patients
0 5 10 15 20 25 30
0
20
40
60
80
100
120
140
Mo
rta
lity
(
)
CURE=Clopidogrel in Unstable angina to prevent Recurrent ischemic Events (study) OASIS=Organization to Assess
Strategies for Ischemic Syndromes (study)
Reproduced with permission from Eikelboom JW et al Circulation 2006114774-782
Major Bleeding During First 30 Days Is Associated With Mortality Meta-analysis of 34146
ACS patients from the randomized OASIS OASIS-2 and CURE trials assessed the
association between bleeding within the first 30 days and death
Without major bleeding
With major bleeding
Days
Mo
rtality
(
)
Days from randomization
0 30 60 90 120 150 180 210 240 270 300 330 360 390
0
5
15
30
10
25
20
Major bleed only (without MI) (n=551)
Both MI and major bleed (n=94)
No MI or major bleed (n=12557)
MI only (without major bleed) (n=611)
Data on file The Medicines Company Parsippany NJ
289
125
86
34
Univariate analysis of 13819 patients from ACUITY
Impact of Non-CABG Major Bleeding and
MI at 30 Days on 1-Year Mortality
Radial Access 798 pts 62
Am Heart J 2009 Jan157(1)164-9 Epub 2008 Nov 6
Am Heart J 2009 Jan157(1)164-9 Epub 2008 Nov 6
Hypothetical mechanisms linking bleeding and mortality
Steg P G et al Eur Heart J 2011321854-
1864
Existing bleeding scores
bull TIMI Laboratory-based (hemoglobin hematocrit decrease)
bull GUSTO Clinical (severity)-based
bull GRACE Simplified laboratory and clinical
bull CURE Major minor (combined clin + lab)
bull ACUITY Major (intracranial-ocular access-site retroperit) lab
bull REPLACE-2 bull ISAR-REACT 3 bull PLATO bull STEEPLE bull CURRENT-OASIS
Thrombolysis conservative
PCI-based
BARC (Bleeding Academic Research Consortium) definitions
Mehran et al Circulation 20111232736-2747
bull Type 0 no evidence of bleeding bull Type 1 bleeding that is not actionable without
need for hospitalization or treatment (eg bruising hematoma nosebleeds etc)
bull Type 2 any clinically overt sign of hemorrhage that is actionable but does not meet criteria for type 3 4 or 5 Must meet at least 1 of following criteria ndash Requires intervention ndash Leads to hospitalization MANEJO MEDICO ndash Prompts evaluation
BARC (Bleeding Academic Research Consortium) definitions
Mehran et al Circulation 20111232736-2747
bull Type 3 clinical laboratory andor imaging evidence of bleeding with healthcare provider responses ndash BARC type 3a
bull any transfusion with overt bleeding bull overt bleeding plus hemoglobin drop ge3 to lt5 gdL
ndash BARC type 3b bull overt bleeding plus hemoglobin drop gt5 gdL bull Cardiac tamponade bull Bleeding requiring surgical intervention for control (excluding dentalnasalskinhemorrhoid) bull Bleeding requiring intravenous vasoactive drugs
ndash BARC type 3c bull Intracranial hemorrhage subcategories confirmed by autopsy
imaging or lumbar puncture bull Intraocular bleed compromising vision
BARC Bleeding Academic Research Consortium) definitions
Mehran et al Circulation 20111232736-2747
bull Type 4 Coronary Artery Bypass Graftndashrelated bleeding ndash Perioperative intracranial bleeding within 48 hours ndash Reoperation after closure of sternotomy for the purpose of controlling bleeding ndash Transfusion of ge5 U whole blood or packed red blood cells within a 48-hour period ndash Chest tube output 2 L within a 24-hour period
bull Type 5 ndash fatal bleeding bull Probable fatal bleeding (type 5a)
ndash bleeding that is clinically suspicious as the cause of death but the bleeding is not directly observed and there is no autopsy or confirmatory imaging
bull Definite fatal bleeding (type 5b) ndash bleeding that is directly observed (by either clinical specimen [blood
emesis stool etc] or imaging) or confirmed on autopsy
26 VCD
11
NSTEACS or STEMI with invasive management Aspirin+P2Y12 blocker
Trans-Femoral Access
Trans-Radial Access
To demonstrate that trans-radial intervention as
compared to femoral access site is associated to lower
rate of the composite endpoint of Death MI or Stroke
within the first 30 days
1deg co-Primary Objective
6 vs 42 βlt10 α 25 8200 patients
Adaptive study Design sample size (SS) will be increased
by the cross-over rate at 70 of planned SS
MATRIX Access site NCT01433627
MATRIX Access
39 93 132 200 276 380 490 685 857 1002 1190
1400 1684 1972 2248
2584 2926
3256 3560
3875 4144
4452 4726
5000 5322
5655 5896 6184
6458 6742 6982 7235 7444 7638 7844 8073
8404
Cumulative enrollment by month
8404
8404
8404 patients with ACS undergoing coronary angiography plusmn PCI from 11th Oct 2011 to 7th Nov 2014
Operator Eligibility Criteria Interventional cardiologist expertise in TRI and TFI including at least 75 transradial coronary interventions and at least 50 of interventions performed via radial route in the year preceding site initiation
Complete follow-up to 30 days available in 4183 (997) of radial and 4191 (99middot6) of femoral cohorts
Am Heart J 2014 Dec168(6)838-45e6
Cross Over and Procedural Success Rates
941 of radial and 974 of femoral cohorts received respective treatment as allocated
In 58 of radial and 23 of TF cohort the allocated access was attempted but failed
In 3 (01) in the radial and 13 (03) patients in the femoral groups the allocated access was not attempted
P=077 Plt0001
TIMI lt3 andor final stenosis gt30
88
103
15 significant reduction at nominal 5 alpha
which is however NOT significant at the pre-specificed
alpha of 25
Primary EP MACE
Femoral
Radial
Rate Ratio 083 95 CI 073 to 096 p=00092
117
98
NNTB 53 Femoral
Radial
Primary EP NACE
Mortalidad Total
IAM
Fatal and ST EPs All-Cause Cardiac non-CV mortality type of stent thrombosis
RR072
(053-099)
P=0045
RR 075
(054-104)
P=008 1
13
06
1
0
02
04
06
08
1
12
14
Radial Femoral
P=069
P=066
Mortality Stent Thrombosis
NNTB 167
Bleeding endpoints BARC TIMI GUSTO access vs non-access related
14
25
P=0013
RR 067 049-092
P=00004
RR 037 021-066
BARC 3 or 5
P=00098
RR 064 045-090
P=008
RR 072 050-104 P=020
RR 078 053-114
Major
or minor
moderate
or severe
P=082
P=068
Rardial Better Femoral Better 1
HAZARD RATIO (95 CI)
P-VALUES
Superiority Interaction
089 Intermediate (548-991)
075 (060-094)
104 (082-132) 076 0011
Centrersquos annual
volume of PCI
Low (247-544)
Intermediate (654-790)
Centrersquos
Proportion of
radial PCI
Low (149-644)
NSTE-ACS (tpndash) ACS type
STEMI
lt75 Age
ge75 023 088 (070-109)
082 (068-097) 0023 062
NACE Subgroup Analysis
High (1000-1950)
High (800-980)
NSTE-ACS (tp+)
Men Sex
Women
lt25 BMI
ge25
No
Ticagrelor or
prasugrel Yes
No Diabetes
Yes
lt60 GFR
ge60
No
History of
PVD Yes
2 025 050
075 (058-097) 0025
00048
101 (079-129)
095 (075 -122) 071
095
064 (051-080) lt0001
044
086 (068-108)
058 (033-103) 0059
019
085 (071-102) 007
0012 072 (056-093)
089 (076-105) 016 018
009 086 (073-102)
079 (063-099) 0038 053
007 083 (068-102)
084 (070-101) 006 094
045 091 (071-117)
080 (068-094) 008 043
001 078 (065-094)
086 (070-107) 018 051
060 091 (064-130)
083 (071-096) 0012 064
Radial Better Femoral Better 1
HAZARD RATIO (95 CI)
P-VALUES
Superiority Interaction
Intermediate (654-790)
Centrersquos
Proportion
of radial PCI
Low (149-644)
NSTE-ACS (tpndash) ACS
type
STEMI
Subgroup Analysis
High (800-980)
NSTE-ACS (tp+)
2
00157
128 (071-232)
069 (040 -119) 018
041
048 (028-081) 0006
010
087 (059-129) 049
049 (028-087) 0012
Intermediate (654-790) Centrersquos
Proportion
of radial PCI
Low (149-644)
NSTE-ACS (tpndash) ACS
type
STEMI
High (800-980)
NSTE-ACS (tp+)
020
090 (054-150)
057 (031 -103) 006
068
056 (032-097) 0035
054
062 (041-094)
166 (028-100) 058
0022
070 (042-117) 017
Mortality
Bleeding
4 050 025
1 2 050 025
Updated Meta-analysis 19328 ACS patients being randomly allocated to radial or femoral access
Rardial Better Femoral Better 1 4 025 050 2
Pre-Rival RIVAL Post-RIVAL MATRI
X Combined
Non-CABG
major bleeds
Death
myocardial
infarction or
stroke
Death
Myocardial
Infarction
Stroke
Pre-Rival RIVAL Post-RIVAL MATRI
X Combined
Pre-Rival RIVAL Post-RIVAL MATRI
X Combined
Pre-Rival RIVAL Post-RIVAL MATRI
X Combined
Pre-Rival RIVAL Post-RIVAL MATRI
X Combined
SUBGROUP Risk Ratio (95CI) P Value
Heterogenity
P Value I2
073 (043-123) 039 (023-067)
058 (046-072)
041 (022-076)
lt00001 0 05
1
067 (048-093) 086 (076-098) 086 (077-095)
098 (076-127)
00051 0 09
7
058 (039-087) 073 (053-099) 072 (060-088) 00011 0 10
0
085 (039-190) 091 (078-106) 091 (079-104)
092 (065-131)
01
6 0 08
8
068 (049-092)
082 (052-129)
077 (046-128) 086 (058-129)
073 (012-447)
140 (045-440) 100 (050-200) 105 (069-160)
143 (072-283)
08
0 0 07
5
026 (006-123)
Summary bull Among patients with an ACS with or without ST-segment
elevation who underwent invasive management the use
of radial access for coronary angiography plusmn PCI reduced
the rate of net adverse clinical events with a number
needed to treat for benefit of 53
ndash Differences between groups were driven by reductions in BARC
major bleeding unrelated to CABG and all-cause mortality with
radial access
bull Our results in conjunction with the updated meta-
analysis suggest that radial approach should
become the default access for patients with
ACS undergoing invasive management
Radial Acces 61000 menos Muertes
LA VIA TRANSRADIAL DEBERIA SER EL ACCESO DE ELECCION o ldquo DEFAULTrdquo PARA LOS PACIENTES CON SCA TRATADOS CON INTERVENCIONISMO PERCUTANEO
LA VIA TRANSRADIAL DEBERIA SER EL ACCESO DE ELECCION PARA TODO PACIENTE CONSIN SCA TRATADOS CON INTERVENCIONISMO PERCUTANEO
GRACIAS POR SU ATENCION
MACE
Mortality
No interaction between access and anticoagulant use in a post- hoc analysis of the subgroup of 7213 patients randomized to bivalirudin or unfractionated heparin for the two co-primary outcomes all-cause mortality or BARC 3 or 5 bleeding
Relevance of bleeding as a clinical endpoint
bull Availability of potent antithrombotic therapy including ndash ASA ndash P2Y12 inhibitors (clopidogrel prasugrel ticagrelor) ndash heparin ndash GP IIbIIIa inhibitors ndash direct thrombin inhibitors
bull has led to a reduction in ischemic events bull but is associated with an increased risk of
bleeding bull the increase in bleeding is associated with worse
clinical outcome
Rationale for a new bleeding definition
bull Increased importance of bleeding as prognostic factor
bull Need for assessment of bleeding in RCTs and registries
bull Lack of comparability bull Need for standardized definitions to avoid
erroneous conclusions
ndash regarding safety of a given agent ndash regarding superiority of one agent over another
Open questions regarding BARC
bull Why 48-hour window for CABG-related bleeding
bull Why type 1 bdquonot actionableldquo when patient may bdquotake actionldquo such as discontinuing medication (with potentially serious consequences such as ST)
bull Why consider intraocular bleed equivalent to intracranial bleed for BARC 3c
bull Type 1 bleed subject to misinterpretation by the patient
Hicks et al (editorial) Circulation 20111232664
Conclusion
bull BARC is a new objective hierarchically graded classification of bleeding
(Mehran Circulation [June 14] 20111232736)
bull BARC is based on consensus rather than data-driven
bull Prospective validation is warranted ndash across the spectrum of IHD
ndash across management strategies (conservative invasive)
ndash in the context of all invasive procedures (PCI CABG endovascular TAVI)
Conclusion (2)
bull Final validation of BARC and proof of its utility depend on
ndash its use by all future RCTs as common safety endpoint
ndash unanimous assessment procedure (questionnaires)
bull More important than using one or the other bleeding risk score is the agreement and commitment among clinical trialists to use the same score for comparability of data
Cine frame from the first selective coronary arteriogram recorded by F Mason Sones Jr on
October 30 1958
Cheng T O Circulation 2003107e42
Copyright copy American Heart Association Inc All rights reserved
EDUCATIONAL CONTENT ENDORSED BY EAPCI A REGISTERED BRANCH
OF THE EUROPEAN SOCIETY OF CARDIOLOGY
Figure 1
copy 2
014 E
uro
pa D
igital amp
Publis
hin
g A
ll rig
hts
reserv
ed
The PCR-EAPCI Textbook ndash Percutaneous interventional cardiovascular medicine
Vascular access Olivier Bertrand Rodney de Palma David Meerkin
EDUCATIONAL CONTENT ENDORSED BY EAPCI A REGISTERED BRANCH
OF THE EUROPEAN SOCIETY OF CARDIOLOGY
Figure 6
copy 2
014 E
uro
pa D
igital amp
Publis
hin
g A
ll rig
hts
reserv
ed
The PCR-EAPCI Textbook ndash Percutaneous interventional cardiovascular medicine
Vascular access Olivier Bertrand Rodney de Palma David Meerkin
Procedimientos INCC 2014
N 1455
Acceso radial en el tratamiento intervencionista del infarto agudo de miocardio con sobreelevacioacuten del ST Dr Gabriel Pintos INCC
OBJETIVO Evaluar los resultados obtenidos en el tratamiento intervencionista de pacientes con IAMcST realizado por acceso radial
MEacuteTODO Estudio analiacutetico de cohorte
Desde el 01012003 hasta el 31122009 se trataron 2114 pacientes con IAMcST en curso (lt24 hs de evolucioacuten) Se incluyeron en la base de datos de la institucioacuten y se registroacute prospectivamente
bull Comorbilidad bull Procedimiento realizado bull Tipo y nuacutemero de arterias tratadas bull Dispositivos utilizados bull Evolucioacuten pos procedimiento inmediata
0
20
40
60
80
100
393 874 96
n꞊280 n꞊657 n꞊1177
Incidencia del acceso radial en IAMcST seguacuten eacutepoca
SUPERVIVENCIA SEGUacuteN ACCESO VASCULAR
p lt 001
diacuteas
AF 057
AR 068
CONCLUSIONES
El ACCESO RADIAL se asocioacute a disminucioacuten del riesgo de
MUERTE a corto y largo plazo en el tratamiento intervencionista
del IAMcST y por tanto PODRIA SER LA VIA DE ABORDAJE DE
ELECCION EN ESTOS PACIENTES
Adoption of Radial Access in PCI in US Trend in the Use of r-PCI Over Time in the Overall amp Key Subgroups
Feldman et al Circulation 20131272295
All Patients
Pts with Stable angina NSTE ACS STEMI
Overall Radial PCI
R
ad
ial
20
07
- Q
tr
20
07
- Q
tr
20
08
- Q
tr
20
08
- Q
tr
20
09
- Q
tr
20
09
- Q
tr
20
10
- Q
tr
20
10
- Q
tr
20
11
- Q
tr
20
11
- Q
tr
20
12
- Q
tr
20
12
- Q
tr
20
18
16
14
12
10
8
6
4
2
161
R
ad
ial
20
07
- Q
tr
20
07
- Q
tr
20
08
- Q
tr
20
08
- Q
tr
20
09
- Q
tr
20
09
- Q
tr
20
10
- Q
tr
20
10
- Q
tr
20
11
- Q
tr
20
11
- Q
tr
20
12
- Q
tr
20
12
- Q
tr
Male Female 20
18
16
14
12
10
8
6
4
2
R
ad
ial
20
07
- Q
tr
20
07
- Q
tr
20
08
- Q
tr
20
08
- Q
tr
20
09
- Q
tr
20
09
- Q
tr
20
10
- Q
tr
20
10
- Q
tr
20
11
- Q
tr
20
11
- Q
tr
20
12
- Q
tr
20
12
- Q
tr
UANSTEMI STEMI Stable Angina 2
0
1
8
1
6
1
4
1
2
1
0
8
6
4
2
IAM
bull All antithrombotic agents (except fondaparinux bivalirudin) are associated with increased bleeding risk
bull Aspirin and heparin reduce death MI at 30 days in NSTE-ACS
Choice of arterial access site and outcomes in patients with acute coronary
siacutendromes managed with an early invasive strategy the ACUITY trial Hamon M Rasmussen LH Manoukian SV Cequier A Lincoff MA Rupprecht HJ Gersh BJ Mann T Bertrand ME Mehran R Stone GW
AIMS The purpose of this study was to evaluate the impact of arterial access site on bleeding and ischaemic outcomes overall and by
treatment strategy in patients with acute coronary syndromes (ACS)
METHODS AND RESULTS In the ACUITY trial 13819 patients with moderate and high-risk ACS were randomised to either heparin
(unfractionated or enoxaparin) plus a glycoprotein IIbIIIa inhibitor (GPI) bivalirudin plus a GPI or bivalirudin alone
Per operator choice femoral access was utilised in 11989 patients (938) and radial Access in 798 patients (62) There was no significant
difference in composite ischaemia between the radial and femoral approaches at 30 days (81 vs 75 p=018) or 1 year (147 vs
155 p=077)although fewer major bleeding complications occurred with the use of radial access (30vs48 p=003) Use of
bivalirudin monotherapy was associated with significantly less 30-day major bleeding than heparin plus GPI after femoral access
(30 vs 58 plt00001) but not with radial access (42 vs 22 P=019)
Major or minor organ bleeding was reduced with bivalirudin monotherapy compared to heparin plus GPI to a similar extent with both
femoral (41 vs 74 Plt00001) and radial (49 vs 72 P=026) access
EuroIntervention 2009 May5(1)115-20
CONCLUSIONS
Transradial compared to femoral arterial access is associated with similar rates of composite ischaemia
anwith fewer major bleeding complications in patients with ACS managed invasively
Bivalirudin monotherapy compared to heparin plus GPIs significantly reduces
access site related major bleeding complications with femoral
but not radial artery access though non-access site related bleeding is reduced by
bivalirudin monotherapy in all patients
0 5 10 15 20 25 30
0
20
40
60
80
100
120
140
Mo
rta
lity
(
)
CURE=Clopidogrel in Unstable angina to prevent Recurrent ischemic Events (study) OASIS=Organization to Assess
Strategies for Ischemic Syndromes (study)
Reproduced with permission from Eikelboom JW et al Circulation 2006114774-782
Major Bleeding During First 30 Days Is Associated With Mortality Meta-analysis of 34146
ACS patients from the randomized OASIS OASIS-2 and CURE trials assessed the
association between bleeding within the first 30 days and death
Without major bleeding
With major bleeding
Days
Mo
rtality
(
)
Days from randomization
0 30 60 90 120 150 180 210 240 270 300 330 360 390
0
5
15
30
10
25
20
Major bleed only (without MI) (n=551)
Both MI and major bleed (n=94)
No MI or major bleed (n=12557)
MI only (without major bleed) (n=611)
Data on file The Medicines Company Parsippany NJ
289
125
86
34
Univariate analysis of 13819 patients from ACUITY
Impact of Non-CABG Major Bleeding and
MI at 30 Days on 1-Year Mortality
Radial Access 798 pts 62
Am Heart J 2009 Jan157(1)164-9 Epub 2008 Nov 6
Am Heart J 2009 Jan157(1)164-9 Epub 2008 Nov 6
Hypothetical mechanisms linking bleeding and mortality
Steg P G et al Eur Heart J 2011321854-
1864
Existing bleeding scores
bull TIMI Laboratory-based (hemoglobin hematocrit decrease)
bull GUSTO Clinical (severity)-based
bull GRACE Simplified laboratory and clinical
bull CURE Major minor (combined clin + lab)
bull ACUITY Major (intracranial-ocular access-site retroperit) lab
bull REPLACE-2 bull ISAR-REACT 3 bull PLATO bull STEEPLE bull CURRENT-OASIS
Thrombolysis conservative
PCI-based
BARC (Bleeding Academic Research Consortium) definitions
Mehran et al Circulation 20111232736-2747
bull Type 0 no evidence of bleeding bull Type 1 bleeding that is not actionable without
need for hospitalization or treatment (eg bruising hematoma nosebleeds etc)
bull Type 2 any clinically overt sign of hemorrhage that is actionable but does not meet criteria for type 3 4 or 5 Must meet at least 1 of following criteria ndash Requires intervention ndash Leads to hospitalization MANEJO MEDICO ndash Prompts evaluation
BARC (Bleeding Academic Research Consortium) definitions
Mehran et al Circulation 20111232736-2747
bull Type 3 clinical laboratory andor imaging evidence of bleeding with healthcare provider responses ndash BARC type 3a
bull any transfusion with overt bleeding bull overt bleeding plus hemoglobin drop ge3 to lt5 gdL
ndash BARC type 3b bull overt bleeding plus hemoglobin drop gt5 gdL bull Cardiac tamponade bull Bleeding requiring surgical intervention for control (excluding dentalnasalskinhemorrhoid) bull Bleeding requiring intravenous vasoactive drugs
ndash BARC type 3c bull Intracranial hemorrhage subcategories confirmed by autopsy
imaging or lumbar puncture bull Intraocular bleed compromising vision
BARC Bleeding Academic Research Consortium) definitions
Mehran et al Circulation 20111232736-2747
bull Type 4 Coronary Artery Bypass Graftndashrelated bleeding ndash Perioperative intracranial bleeding within 48 hours ndash Reoperation after closure of sternotomy for the purpose of controlling bleeding ndash Transfusion of ge5 U whole blood or packed red blood cells within a 48-hour period ndash Chest tube output 2 L within a 24-hour period
bull Type 5 ndash fatal bleeding bull Probable fatal bleeding (type 5a)
ndash bleeding that is clinically suspicious as the cause of death but the bleeding is not directly observed and there is no autopsy or confirmatory imaging
bull Definite fatal bleeding (type 5b) ndash bleeding that is directly observed (by either clinical specimen [blood
emesis stool etc] or imaging) or confirmed on autopsy
26 VCD
11
NSTEACS or STEMI with invasive management Aspirin+P2Y12 blocker
Trans-Femoral Access
Trans-Radial Access
To demonstrate that trans-radial intervention as
compared to femoral access site is associated to lower
rate of the composite endpoint of Death MI or Stroke
within the first 30 days
1deg co-Primary Objective
6 vs 42 βlt10 α 25 8200 patients
Adaptive study Design sample size (SS) will be increased
by the cross-over rate at 70 of planned SS
MATRIX Access site NCT01433627
MATRIX Access
39 93 132 200 276 380 490 685 857 1002 1190
1400 1684 1972 2248
2584 2926
3256 3560
3875 4144
4452 4726
5000 5322
5655 5896 6184
6458 6742 6982 7235 7444 7638 7844 8073
8404
Cumulative enrollment by month
8404
8404
8404 patients with ACS undergoing coronary angiography plusmn PCI from 11th Oct 2011 to 7th Nov 2014
Operator Eligibility Criteria Interventional cardiologist expertise in TRI and TFI including at least 75 transradial coronary interventions and at least 50 of interventions performed via radial route in the year preceding site initiation
Complete follow-up to 30 days available in 4183 (997) of radial and 4191 (99middot6) of femoral cohorts
Am Heart J 2014 Dec168(6)838-45e6
Cross Over and Procedural Success Rates
941 of radial and 974 of femoral cohorts received respective treatment as allocated
In 58 of radial and 23 of TF cohort the allocated access was attempted but failed
In 3 (01) in the radial and 13 (03) patients in the femoral groups the allocated access was not attempted
P=077 Plt0001
TIMI lt3 andor final stenosis gt30
88
103
15 significant reduction at nominal 5 alpha
which is however NOT significant at the pre-specificed
alpha of 25
Primary EP MACE
Femoral
Radial
Rate Ratio 083 95 CI 073 to 096 p=00092
117
98
NNTB 53 Femoral
Radial
Primary EP NACE
Mortalidad Total
IAM
Fatal and ST EPs All-Cause Cardiac non-CV mortality type of stent thrombosis
RR072
(053-099)
P=0045
RR 075
(054-104)
P=008 1
13
06
1
0
02
04
06
08
1
12
14
Radial Femoral
P=069
P=066
Mortality Stent Thrombosis
NNTB 167
Bleeding endpoints BARC TIMI GUSTO access vs non-access related
14
25
P=0013
RR 067 049-092
P=00004
RR 037 021-066
BARC 3 or 5
P=00098
RR 064 045-090
P=008
RR 072 050-104 P=020
RR 078 053-114
Major
or minor
moderate
or severe
P=082
P=068
Rardial Better Femoral Better 1
HAZARD RATIO (95 CI)
P-VALUES
Superiority Interaction
089 Intermediate (548-991)
075 (060-094)
104 (082-132) 076 0011
Centrersquos annual
volume of PCI
Low (247-544)
Intermediate (654-790)
Centrersquos
Proportion of
radial PCI
Low (149-644)
NSTE-ACS (tpndash) ACS type
STEMI
lt75 Age
ge75 023 088 (070-109)
082 (068-097) 0023 062
NACE Subgroup Analysis
High (1000-1950)
High (800-980)
NSTE-ACS (tp+)
Men Sex
Women
lt25 BMI
ge25
No
Ticagrelor or
prasugrel Yes
No Diabetes
Yes
lt60 GFR
ge60
No
History of
PVD Yes
2 025 050
075 (058-097) 0025
00048
101 (079-129)
095 (075 -122) 071
095
064 (051-080) lt0001
044
086 (068-108)
058 (033-103) 0059
019
085 (071-102) 007
0012 072 (056-093)
089 (076-105) 016 018
009 086 (073-102)
079 (063-099) 0038 053
007 083 (068-102)
084 (070-101) 006 094
045 091 (071-117)
080 (068-094) 008 043
001 078 (065-094)
086 (070-107) 018 051
060 091 (064-130)
083 (071-096) 0012 064
Radial Better Femoral Better 1
HAZARD RATIO (95 CI)
P-VALUES
Superiority Interaction
Intermediate (654-790)
Centrersquos
Proportion
of radial PCI
Low (149-644)
NSTE-ACS (tpndash) ACS
type
STEMI
Subgroup Analysis
High (800-980)
NSTE-ACS (tp+)
2
00157
128 (071-232)
069 (040 -119) 018
041
048 (028-081) 0006
010
087 (059-129) 049
049 (028-087) 0012
Intermediate (654-790) Centrersquos
Proportion
of radial PCI
Low (149-644)
NSTE-ACS (tpndash) ACS
type
STEMI
High (800-980)
NSTE-ACS (tp+)
020
090 (054-150)
057 (031 -103) 006
068
056 (032-097) 0035
054
062 (041-094)
166 (028-100) 058
0022
070 (042-117) 017
Mortality
Bleeding
4 050 025
1 2 050 025
Updated Meta-analysis 19328 ACS patients being randomly allocated to radial or femoral access
Rardial Better Femoral Better 1 4 025 050 2
Pre-Rival RIVAL Post-RIVAL MATRI
X Combined
Non-CABG
major bleeds
Death
myocardial
infarction or
stroke
Death
Myocardial
Infarction
Stroke
Pre-Rival RIVAL Post-RIVAL MATRI
X Combined
Pre-Rival RIVAL Post-RIVAL MATRI
X Combined
Pre-Rival RIVAL Post-RIVAL MATRI
X Combined
Pre-Rival RIVAL Post-RIVAL MATRI
X Combined
SUBGROUP Risk Ratio (95CI) P Value
Heterogenity
P Value I2
073 (043-123) 039 (023-067)
058 (046-072)
041 (022-076)
lt00001 0 05
1
067 (048-093) 086 (076-098) 086 (077-095)
098 (076-127)
00051 0 09
7
058 (039-087) 073 (053-099) 072 (060-088) 00011 0 10
0
085 (039-190) 091 (078-106) 091 (079-104)
092 (065-131)
01
6 0 08
8
068 (049-092)
082 (052-129)
077 (046-128) 086 (058-129)
073 (012-447)
140 (045-440) 100 (050-200) 105 (069-160)
143 (072-283)
08
0 0 07
5
026 (006-123)
Summary bull Among patients with an ACS with or without ST-segment
elevation who underwent invasive management the use
of radial access for coronary angiography plusmn PCI reduced
the rate of net adverse clinical events with a number
needed to treat for benefit of 53
ndash Differences between groups were driven by reductions in BARC
major bleeding unrelated to CABG and all-cause mortality with
radial access
bull Our results in conjunction with the updated meta-
analysis suggest that radial approach should
become the default access for patients with
ACS undergoing invasive management
Radial Acces 61000 menos Muertes
LA VIA TRANSRADIAL DEBERIA SER EL ACCESO DE ELECCION o ldquo DEFAULTrdquo PARA LOS PACIENTES CON SCA TRATADOS CON INTERVENCIONISMO PERCUTANEO
LA VIA TRANSRADIAL DEBERIA SER EL ACCESO DE ELECCION PARA TODO PACIENTE CONSIN SCA TRATADOS CON INTERVENCIONISMO PERCUTANEO
GRACIAS POR SU ATENCION
MACE
Mortality
No interaction between access and anticoagulant use in a post- hoc analysis of the subgroup of 7213 patients randomized to bivalirudin or unfractionated heparin for the two co-primary outcomes all-cause mortality or BARC 3 or 5 bleeding
Relevance of bleeding as a clinical endpoint
bull Availability of potent antithrombotic therapy including ndash ASA ndash P2Y12 inhibitors (clopidogrel prasugrel ticagrelor) ndash heparin ndash GP IIbIIIa inhibitors ndash direct thrombin inhibitors
bull has led to a reduction in ischemic events bull but is associated with an increased risk of
bleeding bull the increase in bleeding is associated with worse
clinical outcome
Rationale for a new bleeding definition
bull Increased importance of bleeding as prognostic factor
bull Need for assessment of bleeding in RCTs and registries
bull Lack of comparability bull Need for standardized definitions to avoid
erroneous conclusions
ndash regarding safety of a given agent ndash regarding superiority of one agent over another
Open questions regarding BARC
bull Why 48-hour window for CABG-related bleeding
bull Why type 1 bdquonot actionableldquo when patient may bdquotake actionldquo such as discontinuing medication (with potentially serious consequences such as ST)
bull Why consider intraocular bleed equivalent to intracranial bleed for BARC 3c
bull Type 1 bleed subject to misinterpretation by the patient
Hicks et al (editorial) Circulation 20111232664
Conclusion
bull BARC is a new objective hierarchically graded classification of bleeding
(Mehran Circulation [June 14] 20111232736)
bull BARC is based on consensus rather than data-driven
bull Prospective validation is warranted ndash across the spectrum of IHD
ndash across management strategies (conservative invasive)
ndash in the context of all invasive procedures (PCI CABG endovascular TAVI)
Conclusion (2)
bull Final validation of BARC and proof of its utility depend on
ndash its use by all future RCTs as common safety endpoint
ndash unanimous assessment procedure (questionnaires)
bull More important than using one or the other bleeding risk score is the agreement and commitment among clinical trialists to use the same score for comparability of data
EDUCATIONAL CONTENT ENDORSED BY EAPCI A REGISTERED BRANCH
OF THE EUROPEAN SOCIETY OF CARDIOLOGY
Figure 1
copy 2
014 E
uro
pa D
igital amp
Publis
hin
g A
ll rig
hts
reserv
ed
The PCR-EAPCI Textbook ndash Percutaneous interventional cardiovascular medicine
Vascular access Olivier Bertrand Rodney de Palma David Meerkin
EDUCATIONAL CONTENT ENDORSED BY EAPCI A REGISTERED BRANCH
OF THE EUROPEAN SOCIETY OF CARDIOLOGY
Figure 6
copy 2
014 E
uro
pa D
igital amp
Publis
hin
g A
ll rig
hts
reserv
ed
The PCR-EAPCI Textbook ndash Percutaneous interventional cardiovascular medicine
Vascular access Olivier Bertrand Rodney de Palma David Meerkin
Procedimientos INCC 2014
N 1455
Acceso radial en el tratamiento intervencionista del infarto agudo de miocardio con sobreelevacioacuten del ST Dr Gabriel Pintos INCC
OBJETIVO Evaluar los resultados obtenidos en el tratamiento intervencionista de pacientes con IAMcST realizado por acceso radial
MEacuteTODO Estudio analiacutetico de cohorte
Desde el 01012003 hasta el 31122009 se trataron 2114 pacientes con IAMcST en curso (lt24 hs de evolucioacuten) Se incluyeron en la base de datos de la institucioacuten y se registroacute prospectivamente
bull Comorbilidad bull Procedimiento realizado bull Tipo y nuacutemero de arterias tratadas bull Dispositivos utilizados bull Evolucioacuten pos procedimiento inmediata
0
20
40
60
80
100
393 874 96
n꞊280 n꞊657 n꞊1177
Incidencia del acceso radial en IAMcST seguacuten eacutepoca
SUPERVIVENCIA SEGUacuteN ACCESO VASCULAR
p lt 001
diacuteas
AF 057
AR 068
CONCLUSIONES
El ACCESO RADIAL se asocioacute a disminucioacuten del riesgo de
MUERTE a corto y largo plazo en el tratamiento intervencionista
del IAMcST y por tanto PODRIA SER LA VIA DE ABORDAJE DE
ELECCION EN ESTOS PACIENTES
Adoption of Radial Access in PCI in US Trend in the Use of r-PCI Over Time in the Overall amp Key Subgroups
Feldman et al Circulation 20131272295
All Patients
Pts with Stable angina NSTE ACS STEMI
Overall Radial PCI
R
ad
ial
20
07
- Q
tr
20
07
- Q
tr
20
08
- Q
tr
20
08
- Q
tr
20
09
- Q
tr
20
09
- Q
tr
20
10
- Q
tr
20
10
- Q
tr
20
11
- Q
tr
20
11
- Q
tr
20
12
- Q
tr
20
12
- Q
tr
20
18
16
14
12
10
8
6
4
2
161
R
ad
ial
20
07
- Q
tr
20
07
- Q
tr
20
08
- Q
tr
20
08
- Q
tr
20
09
- Q
tr
20
09
- Q
tr
20
10
- Q
tr
20
10
- Q
tr
20
11
- Q
tr
20
11
- Q
tr
20
12
- Q
tr
20
12
- Q
tr
Male Female 20
18
16
14
12
10
8
6
4
2
R
ad
ial
20
07
- Q
tr
20
07
- Q
tr
20
08
- Q
tr
20
08
- Q
tr
20
09
- Q
tr
20
09
- Q
tr
20
10
- Q
tr
20
10
- Q
tr
20
11
- Q
tr
20
11
- Q
tr
20
12
- Q
tr
20
12
- Q
tr
UANSTEMI STEMI Stable Angina 2
0
1
8
1
6
1
4
1
2
1
0
8
6
4
2
IAM
bull All antithrombotic agents (except fondaparinux bivalirudin) are associated with increased bleeding risk
bull Aspirin and heparin reduce death MI at 30 days in NSTE-ACS
Choice of arterial access site and outcomes in patients with acute coronary
siacutendromes managed with an early invasive strategy the ACUITY trial Hamon M Rasmussen LH Manoukian SV Cequier A Lincoff MA Rupprecht HJ Gersh BJ Mann T Bertrand ME Mehran R Stone GW
AIMS The purpose of this study was to evaluate the impact of arterial access site on bleeding and ischaemic outcomes overall and by
treatment strategy in patients with acute coronary syndromes (ACS)
METHODS AND RESULTS In the ACUITY trial 13819 patients with moderate and high-risk ACS were randomised to either heparin
(unfractionated or enoxaparin) plus a glycoprotein IIbIIIa inhibitor (GPI) bivalirudin plus a GPI or bivalirudin alone
Per operator choice femoral access was utilised in 11989 patients (938) and radial Access in 798 patients (62) There was no significant
difference in composite ischaemia between the radial and femoral approaches at 30 days (81 vs 75 p=018) or 1 year (147 vs
155 p=077)although fewer major bleeding complications occurred with the use of radial access (30vs48 p=003) Use of
bivalirudin monotherapy was associated with significantly less 30-day major bleeding than heparin plus GPI after femoral access
(30 vs 58 plt00001) but not with radial access (42 vs 22 P=019)
Major or minor organ bleeding was reduced with bivalirudin monotherapy compared to heparin plus GPI to a similar extent with both
femoral (41 vs 74 Plt00001) and radial (49 vs 72 P=026) access
EuroIntervention 2009 May5(1)115-20
CONCLUSIONS
Transradial compared to femoral arterial access is associated with similar rates of composite ischaemia
anwith fewer major bleeding complications in patients with ACS managed invasively
Bivalirudin monotherapy compared to heparin plus GPIs significantly reduces
access site related major bleeding complications with femoral
but not radial artery access though non-access site related bleeding is reduced by
bivalirudin monotherapy in all patients
0 5 10 15 20 25 30
0
20
40
60
80
100
120
140
Mo
rta
lity
(
)
CURE=Clopidogrel in Unstable angina to prevent Recurrent ischemic Events (study) OASIS=Organization to Assess
Strategies for Ischemic Syndromes (study)
Reproduced with permission from Eikelboom JW et al Circulation 2006114774-782
Major Bleeding During First 30 Days Is Associated With Mortality Meta-analysis of 34146
ACS patients from the randomized OASIS OASIS-2 and CURE trials assessed the
association between bleeding within the first 30 days and death
Without major bleeding
With major bleeding
Days
Mo
rtality
(
)
Days from randomization
0 30 60 90 120 150 180 210 240 270 300 330 360 390
0
5
15
30
10
25
20
Major bleed only (without MI) (n=551)
Both MI and major bleed (n=94)
No MI or major bleed (n=12557)
MI only (without major bleed) (n=611)
Data on file The Medicines Company Parsippany NJ
289
125
86
34
Univariate analysis of 13819 patients from ACUITY
Impact of Non-CABG Major Bleeding and
MI at 30 Days on 1-Year Mortality
Radial Access 798 pts 62
Am Heart J 2009 Jan157(1)164-9 Epub 2008 Nov 6
Am Heart J 2009 Jan157(1)164-9 Epub 2008 Nov 6
Hypothetical mechanisms linking bleeding and mortality
Steg P G et al Eur Heart J 2011321854-
1864
Existing bleeding scores
bull TIMI Laboratory-based (hemoglobin hematocrit decrease)
bull GUSTO Clinical (severity)-based
bull GRACE Simplified laboratory and clinical
bull CURE Major minor (combined clin + lab)
bull ACUITY Major (intracranial-ocular access-site retroperit) lab
bull REPLACE-2 bull ISAR-REACT 3 bull PLATO bull STEEPLE bull CURRENT-OASIS
Thrombolysis conservative
PCI-based
BARC (Bleeding Academic Research Consortium) definitions
Mehran et al Circulation 20111232736-2747
bull Type 0 no evidence of bleeding bull Type 1 bleeding that is not actionable without
need for hospitalization or treatment (eg bruising hematoma nosebleeds etc)
bull Type 2 any clinically overt sign of hemorrhage that is actionable but does not meet criteria for type 3 4 or 5 Must meet at least 1 of following criteria ndash Requires intervention ndash Leads to hospitalization MANEJO MEDICO ndash Prompts evaluation
BARC (Bleeding Academic Research Consortium) definitions
Mehran et al Circulation 20111232736-2747
bull Type 3 clinical laboratory andor imaging evidence of bleeding with healthcare provider responses ndash BARC type 3a
bull any transfusion with overt bleeding bull overt bleeding plus hemoglobin drop ge3 to lt5 gdL
ndash BARC type 3b bull overt bleeding plus hemoglobin drop gt5 gdL bull Cardiac tamponade bull Bleeding requiring surgical intervention for control (excluding dentalnasalskinhemorrhoid) bull Bleeding requiring intravenous vasoactive drugs
ndash BARC type 3c bull Intracranial hemorrhage subcategories confirmed by autopsy
imaging or lumbar puncture bull Intraocular bleed compromising vision
BARC Bleeding Academic Research Consortium) definitions
Mehran et al Circulation 20111232736-2747
bull Type 4 Coronary Artery Bypass Graftndashrelated bleeding ndash Perioperative intracranial bleeding within 48 hours ndash Reoperation after closure of sternotomy for the purpose of controlling bleeding ndash Transfusion of ge5 U whole blood or packed red blood cells within a 48-hour period ndash Chest tube output 2 L within a 24-hour period
bull Type 5 ndash fatal bleeding bull Probable fatal bleeding (type 5a)
ndash bleeding that is clinically suspicious as the cause of death but the bleeding is not directly observed and there is no autopsy or confirmatory imaging
bull Definite fatal bleeding (type 5b) ndash bleeding that is directly observed (by either clinical specimen [blood
emesis stool etc] or imaging) or confirmed on autopsy
26 VCD
11
NSTEACS or STEMI with invasive management Aspirin+P2Y12 blocker
Trans-Femoral Access
Trans-Radial Access
To demonstrate that trans-radial intervention as
compared to femoral access site is associated to lower
rate of the composite endpoint of Death MI or Stroke
within the first 30 days
1deg co-Primary Objective
6 vs 42 βlt10 α 25 8200 patients
Adaptive study Design sample size (SS) will be increased
by the cross-over rate at 70 of planned SS
MATRIX Access site NCT01433627
MATRIX Access
39 93 132 200 276 380 490 685 857 1002 1190
1400 1684 1972 2248
2584 2926
3256 3560
3875 4144
4452 4726
5000 5322
5655 5896 6184
6458 6742 6982 7235 7444 7638 7844 8073
8404
Cumulative enrollment by month
8404
8404
8404 patients with ACS undergoing coronary angiography plusmn PCI from 11th Oct 2011 to 7th Nov 2014
Operator Eligibility Criteria Interventional cardiologist expertise in TRI and TFI including at least 75 transradial coronary interventions and at least 50 of interventions performed via radial route in the year preceding site initiation
Complete follow-up to 30 days available in 4183 (997) of radial and 4191 (99middot6) of femoral cohorts
Am Heart J 2014 Dec168(6)838-45e6
Cross Over and Procedural Success Rates
941 of radial and 974 of femoral cohorts received respective treatment as allocated
In 58 of radial and 23 of TF cohort the allocated access was attempted but failed
In 3 (01) in the radial and 13 (03) patients in the femoral groups the allocated access was not attempted
P=077 Plt0001
TIMI lt3 andor final stenosis gt30
88
103
15 significant reduction at nominal 5 alpha
which is however NOT significant at the pre-specificed
alpha of 25
Primary EP MACE
Femoral
Radial
Rate Ratio 083 95 CI 073 to 096 p=00092
117
98
NNTB 53 Femoral
Radial
Primary EP NACE
Mortalidad Total
IAM
Fatal and ST EPs All-Cause Cardiac non-CV mortality type of stent thrombosis
RR072
(053-099)
P=0045
RR 075
(054-104)
P=008 1
13
06
1
0
02
04
06
08
1
12
14
Radial Femoral
P=069
P=066
Mortality Stent Thrombosis
NNTB 167
Bleeding endpoints BARC TIMI GUSTO access vs non-access related
14
25
P=0013
RR 067 049-092
P=00004
RR 037 021-066
BARC 3 or 5
P=00098
RR 064 045-090
P=008
RR 072 050-104 P=020
RR 078 053-114
Major
or minor
moderate
or severe
P=082
P=068
Rardial Better Femoral Better 1
HAZARD RATIO (95 CI)
P-VALUES
Superiority Interaction
089 Intermediate (548-991)
075 (060-094)
104 (082-132) 076 0011
Centrersquos annual
volume of PCI
Low (247-544)
Intermediate (654-790)
Centrersquos
Proportion of
radial PCI
Low (149-644)
NSTE-ACS (tpndash) ACS type
STEMI
lt75 Age
ge75 023 088 (070-109)
082 (068-097) 0023 062
NACE Subgroup Analysis
High (1000-1950)
High (800-980)
NSTE-ACS (tp+)
Men Sex
Women
lt25 BMI
ge25
No
Ticagrelor or
prasugrel Yes
No Diabetes
Yes
lt60 GFR
ge60
No
History of
PVD Yes
2 025 050
075 (058-097) 0025
00048
101 (079-129)
095 (075 -122) 071
095
064 (051-080) lt0001
044
086 (068-108)
058 (033-103) 0059
019
085 (071-102) 007
0012 072 (056-093)
089 (076-105) 016 018
009 086 (073-102)
079 (063-099) 0038 053
007 083 (068-102)
084 (070-101) 006 094
045 091 (071-117)
080 (068-094) 008 043
001 078 (065-094)
086 (070-107) 018 051
060 091 (064-130)
083 (071-096) 0012 064
Radial Better Femoral Better 1
HAZARD RATIO (95 CI)
P-VALUES
Superiority Interaction
Intermediate (654-790)
Centrersquos
Proportion
of radial PCI
Low (149-644)
NSTE-ACS (tpndash) ACS
type
STEMI
Subgroup Analysis
High (800-980)
NSTE-ACS (tp+)
2
00157
128 (071-232)
069 (040 -119) 018
041
048 (028-081) 0006
010
087 (059-129) 049
049 (028-087) 0012
Intermediate (654-790) Centrersquos
Proportion
of radial PCI
Low (149-644)
NSTE-ACS (tpndash) ACS
type
STEMI
High (800-980)
NSTE-ACS (tp+)
020
090 (054-150)
057 (031 -103) 006
068
056 (032-097) 0035
054
062 (041-094)
166 (028-100) 058
0022
070 (042-117) 017
Mortality
Bleeding
4 050 025
1 2 050 025
Updated Meta-analysis 19328 ACS patients being randomly allocated to radial or femoral access
Rardial Better Femoral Better 1 4 025 050 2
Pre-Rival RIVAL Post-RIVAL MATRI
X Combined
Non-CABG
major bleeds
Death
myocardial
infarction or
stroke
Death
Myocardial
Infarction
Stroke
Pre-Rival RIVAL Post-RIVAL MATRI
X Combined
Pre-Rival RIVAL Post-RIVAL MATRI
X Combined
Pre-Rival RIVAL Post-RIVAL MATRI
X Combined
Pre-Rival RIVAL Post-RIVAL MATRI
X Combined
SUBGROUP Risk Ratio (95CI) P Value
Heterogenity
P Value I2
073 (043-123) 039 (023-067)
058 (046-072)
041 (022-076)
lt00001 0 05
1
067 (048-093) 086 (076-098) 086 (077-095)
098 (076-127)
00051 0 09
7
058 (039-087) 073 (053-099) 072 (060-088) 00011 0 10
0
085 (039-190) 091 (078-106) 091 (079-104)
092 (065-131)
01
6 0 08
8
068 (049-092)
082 (052-129)
077 (046-128) 086 (058-129)
073 (012-447)
140 (045-440) 100 (050-200) 105 (069-160)
143 (072-283)
08
0 0 07
5
026 (006-123)
Summary bull Among patients with an ACS with or without ST-segment
elevation who underwent invasive management the use
of radial access for coronary angiography plusmn PCI reduced
the rate of net adverse clinical events with a number
needed to treat for benefit of 53
ndash Differences between groups were driven by reductions in BARC
major bleeding unrelated to CABG and all-cause mortality with
radial access
bull Our results in conjunction with the updated meta-
analysis suggest that radial approach should
become the default access for patients with
ACS undergoing invasive management
Radial Acces 61000 menos Muertes
LA VIA TRANSRADIAL DEBERIA SER EL ACCESO DE ELECCION o ldquo DEFAULTrdquo PARA LOS PACIENTES CON SCA TRATADOS CON INTERVENCIONISMO PERCUTANEO
LA VIA TRANSRADIAL DEBERIA SER EL ACCESO DE ELECCION PARA TODO PACIENTE CONSIN SCA TRATADOS CON INTERVENCIONISMO PERCUTANEO
GRACIAS POR SU ATENCION
MACE
Mortality
No interaction between access and anticoagulant use in a post- hoc analysis of the subgroup of 7213 patients randomized to bivalirudin or unfractionated heparin for the two co-primary outcomes all-cause mortality or BARC 3 or 5 bleeding
Relevance of bleeding as a clinical endpoint
bull Availability of potent antithrombotic therapy including ndash ASA ndash P2Y12 inhibitors (clopidogrel prasugrel ticagrelor) ndash heparin ndash GP IIbIIIa inhibitors ndash direct thrombin inhibitors
bull has led to a reduction in ischemic events bull but is associated with an increased risk of
bleeding bull the increase in bleeding is associated with worse
clinical outcome
Rationale for a new bleeding definition
bull Increased importance of bleeding as prognostic factor
bull Need for assessment of bleeding in RCTs and registries
bull Lack of comparability bull Need for standardized definitions to avoid
erroneous conclusions
ndash regarding safety of a given agent ndash regarding superiority of one agent over another
Open questions regarding BARC
bull Why 48-hour window for CABG-related bleeding
bull Why type 1 bdquonot actionableldquo when patient may bdquotake actionldquo such as discontinuing medication (with potentially serious consequences such as ST)
bull Why consider intraocular bleed equivalent to intracranial bleed for BARC 3c
bull Type 1 bleed subject to misinterpretation by the patient
Hicks et al (editorial) Circulation 20111232664
Conclusion
bull BARC is a new objective hierarchically graded classification of bleeding
(Mehran Circulation [June 14] 20111232736)
bull BARC is based on consensus rather than data-driven
bull Prospective validation is warranted ndash across the spectrum of IHD
ndash across management strategies (conservative invasive)
ndash in the context of all invasive procedures (PCI CABG endovascular TAVI)
Conclusion (2)
bull Final validation of BARC and proof of its utility depend on
ndash its use by all future RCTs as common safety endpoint
ndash unanimous assessment procedure (questionnaires)
bull More important than using one or the other bleeding risk score is the agreement and commitment among clinical trialists to use the same score for comparability of data
EDUCATIONAL CONTENT ENDORSED BY EAPCI A REGISTERED BRANCH
OF THE EUROPEAN SOCIETY OF CARDIOLOGY
Figure 6
copy 2
014 E
uro
pa D
igital amp
Publis
hin
g A
ll rig
hts
reserv
ed
The PCR-EAPCI Textbook ndash Percutaneous interventional cardiovascular medicine
Vascular access Olivier Bertrand Rodney de Palma David Meerkin
Procedimientos INCC 2014
N 1455
Acceso radial en el tratamiento intervencionista del infarto agudo de miocardio con sobreelevacioacuten del ST Dr Gabriel Pintos INCC
OBJETIVO Evaluar los resultados obtenidos en el tratamiento intervencionista de pacientes con IAMcST realizado por acceso radial
MEacuteTODO Estudio analiacutetico de cohorte
Desde el 01012003 hasta el 31122009 se trataron 2114 pacientes con IAMcST en curso (lt24 hs de evolucioacuten) Se incluyeron en la base de datos de la institucioacuten y se registroacute prospectivamente
bull Comorbilidad bull Procedimiento realizado bull Tipo y nuacutemero de arterias tratadas bull Dispositivos utilizados bull Evolucioacuten pos procedimiento inmediata
0
20
40
60
80
100
393 874 96
n꞊280 n꞊657 n꞊1177
Incidencia del acceso radial en IAMcST seguacuten eacutepoca
SUPERVIVENCIA SEGUacuteN ACCESO VASCULAR
p lt 001
diacuteas
AF 057
AR 068
CONCLUSIONES
El ACCESO RADIAL se asocioacute a disminucioacuten del riesgo de
MUERTE a corto y largo plazo en el tratamiento intervencionista
del IAMcST y por tanto PODRIA SER LA VIA DE ABORDAJE DE
ELECCION EN ESTOS PACIENTES
Adoption of Radial Access in PCI in US Trend in the Use of r-PCI Over Time in the Overall amp Key Subgroups
Feldman et al Circulation 20131272295
All Patients
Pts with Stable angina NSTE ACS STEMI
Overall Radial PCI
R
ad
ial
20
07
- Q
tr
20
07
- Q
tr
20
08
- Q
tr
20
08
- Q
tr
20
09
- Q
tr
20
09
- Q
tr
20
10
- Q
tr
20
10
- Q
tr
20
11
- Q
tr
20
11
- Q
tr
20
12
- Q
tr
20
12
- Q
tr
20
18
16
14
12
10
8
6
4
2
161
R
ad
ial
20
07
- Q
tr
20
07
- Q
tr
20
08
- Q
tr
20
08
- Q
tr
20
09
- Q
tr
20
09
- Q
tr
20
10
- Q
tr
20
10
- Q
tr
20
11
- Q
tr
20
11
- Q
tr
20
12
- Q
tr
20
12
- Q
tr
Male Female 20
18
16
14
12
10
8
6
4
2
R
ad
ial
20
07
- Q
tr
20
07
- Q
tr
20
08
- Q
tr
20
08
- Q
tr
20
09
- Q
tr
20
09
- Q
tr
20
10
- Q
tr
20
10
- Q
tr
20
11
- Q
tr
20
11
- Q
tr
20
12
- Q
tr
20
12
- Q
tr
UANSTEMI STEMI Stable Angina 2
0
1
8
1
6
1
4
1
2
1
0
8
6
4
2
IAM
bull All antithrombotic agents (except fondaparinux bivalirudin) are associated with increased bleeding risk
bull Aspirin and heparin reduce death MI at 30 days in NSTE-ACS
Choice of arterial access site and outcomes in patients with acute coronary
siacutendromes managed with an early invasive strategy the ACUITY trial Hamon M Rasmussen LH Manoukian SV Cequier A Lincoff MA Rupprecht HJ Gersh BJ Mann T Bertrand ME Mehran R Stone GW
AIMS The purpose of this study was to evaluate the impact of arterial access site on bleeding and ischaemic outcomes overall and by
treatment strategy in patients with acute coronary syndromes (ACS)
METHODS AND RESULTS In the ACUITY trial 13819 patients with moderate and high-risk ACS were randomised to either heparin
(unfractionated or enoxaparin) plus a glycoprotein IIbIIIa inhibitor (GPI) bivalirudin plus a GPI or bivalirudin alone
Per operator choice femoral access was utilised in 11989 patients (938) and radial Access in 798 patients (62) There was no significant
difference in composite ischaemia between the radial and femoral approaches at 30 days (81 vs 75 p=018) or 1 year (147 vs
155 p=077)although fewer major bleeding complications occurred with the use of radial access (30vs48 p=003) Use of
bivalirudin monotherapy was associated with significantly less 30-day major bleeding than heparin plus GPI after femoral access
(30 vs 58 plt00001) but not with radial access (42 vs 22 P=019)
Major or minor organ bleeding was reduced with bivalirudin monotherapy compared to heparin plus GPI to a similar extent with both
femoral (41 vs 74 Plt00001) and radial (49 vs 72 P=026) access
EuroIntervention 2009 May5(1)115-20
CONCLUSIONS
Transradial compared to femoral arterial access is associated with similar rates of composite ischaemia
anwith fewer major bleeding complications in patients with ACS managed invasively
Bivalirudin monotherapy compared to heparin plus GPIs significantly reduces
access site related major bleeding complications with femoral
but not radial artery access though non-access site related bleeding is reduced by
bivalirudin monotherapy in all patients
0 5 10 15 20 25 30
0
20
40
60
80
100
120
140
Mo
rta
lity
(
)
CURE=Clopidogrel in Unstable angina to prevent Recurrent ischemic Events (study) OASIS=Organization to Assess
Strategies for Ischemic Syndromes (study)
Reproduced with permission from Eikelboom JW et al Circulation 2006114774-782
Major Bleeding During First 30 Days Is Associated With Mortality Meta-analysis of 34146
ACS patients from the randomized OASIS OASIS-2 and CURE trials assessed the
association between bleeding within the first 30 days and death
Without major bleeding
With major bleeding
Days
Mo
rtality
(
)
Days from randomization
0 30 60 90 120 150 180 210 240 270 300 330 360 390
0
5
15
30
10
25
20
Major bleed only (without MI) (n=551)
Both MI and major bleed (n=94)
No MI or major bleed (n=12557)
MI only (without major bleed) (n=611)
Data on file The Medicines Company Parsippany NJ
289
125
86
34
Univariate analysis of 13819 patients from ACUITY
Impact of Non-CABG Major Bleeding and
MI at 30 Days on 1-Year Mortality
Radial Access 798 pts 62
Am Heart J 2009 Jan157(1)164-9 Epub 2008 Nov 6
Am Heart J 2009 Jan157(1)164-9 Epub 2008 Nov 6
Hypothetical mechanisms linking bleeding and mortality
Steg P G et al Eur Heart J 2011321854-
1864
Existing bleeding scores
bull TIMI Laboratory-based (hemoglobin hematocrit decrease)
bull GUSTO Clinical (severity)-based
bull GRACE Simplified laboratory and clinical
bull CURE Major minor (combined clin + lab)
bull ACUITY Major (intracranial-ocular access-site retroperit) lab
bull REPLACE-2 bull ISAR-REACT 3 bull PLATO bull STEEPLE bull CURRENT-OASIS
Thrombolysis conservative
PCI-based
BARC (Bleeding Academic Research Consortium) definitions
Mehran et al Circulation 20111232736-2747
bull Type 0 no evidence of bleeding bull Type 1 bleeding that is not actionable without
need for hospitalization or treatment (eg bruising hematoma nosebleeds etc)
bull Type 2 any clinically overt sign of hemorrhage that is actionable but does not meet criteria for type 3 4 or 5 Must meet at least 1 of following criteria ndash Requires intervention ndash Leads to hospitalization MANEJO MEDICO ndash Prompts evaluation
BARC (Bleeding Academic Research Consortium) definitions
Mehran et al Circulation 20111232736-2747
bull Type 3 clinical laboratory andor imaging evidence of bleeding with healthcare provider responses ndash BARC type 3a
bull any transfusion with overt bleeding bull overt bleeding plus hemoglobin drop ge3 to lt5 gdL
ndash BARC type 3b bull overt bleeding plus hemoglobin drop gt5 gdL bull Cardiac tamponade bull Bleeding requiring surgical intervention for control (excluding dentalnasalskinhemorrhoid) bull Bleeding requiring intravenous vasoactive drugs
ndash BARC type 3c bull Intracranial hemorrhage subcategories confirmed by autopsy
imaging or lumbar puncture bull Intraocular bleed compromising vision
BARC Bleeding Academic Research Consortium) definitions
Mehran et al Circulation 20111232736-2747
bull Type 4 Coronary Artery Bypass Graftndashrelated bleeding ndash Perioperative intracranial bleeding within 48 hours ndash Reoperation after closure of sternotomy for the purpose of controlling bleeding ndash Transfusion of ge5 U whole blood or packed red blood cells within a 48-hour period ndash Chest tube output 2 L within a 24-hour period
bull Type 5 ndash fatal bleeding bull Probable fatal bleeding (type 5a)
ndash bleeding that is clinically suspicious as the cause of death but the bleeding is not directly observed and there is no autopsy or confirmatory imaging
bull Definite fatal bleeding (type 5b) ndash bleeding that is directly observed (by either clinical specimen [blood
emesis stool etc] or imaging) or confirmed on autopsy
26 VCD
11
NSTEACS or STEMI with invasive management Aspirin+P2Y12 blocker
Trans-Femoral Access
Trans-Radial Access
To demonstrate that trans-radial intervention as
compared to femoral access site is associated to lower
rate of the composite endpoint of Death MI or Stroke
within the first 30 days
1deg co-Primary Objective
6 vs 42 βlt10 α 25 8200 patients
Adaptive study Design sample size (SS) will be increased
by the cross-over rate at 70 of planned SS
MATRIX Access site NCT01433627
MATRIX Access
39 93 132 200 276 380 490 685 857 1002 1190
1400 1684 1972 2248
2584 2926
3256 3560
3875 4144
4452 4726
5000 5322
5655 5896 6184
6458 6742 6982 7235 7444 7638 7844 8073
8404
Cumulative enrollment by month
8404
8404
8404 patients with ACS undergoing coronary angiography plusmn PCI from 11th Oct 2011 to 7th Nov 2014
Operator Eligibility Criteria Interventional cardiologist expertise in TRI and TFI including at least 75 transradial coronary interventions and at least 50 of interventions performed via radial route in the year preceding site initiation
Complete follow-up to 30 days available in 4183 (997) of radial and 4191 (99middot6) of femoral cohorts
Am Heart J 2014 Dec168(6)838-45e6
Cross Over and Procedural Success Rates
941 of radial and 974 of femoral cohorts received respective treatment as allocated
In 58 of radial and 23 of TF cohort the allocated access was attempted but failed
In 3 (01) in the radial and 13 (03) patients in the femoral groups the allocated access was not attempted
P=077 Plt0001
TIMI lt3 andor final stenosis gt30
88
103
15 significant reduction at nominal 5 alpha
which is however NOT significant at the pre-specificed
alpha of 25
Primary EP MACE
Femoral
Radial
Rate Ratio 083 95 CI 073 to 096 p=00092
117
98
NNTB 53 Femoral
Radial
Primary EP NACE
Mortalidad Total
IAM
Fatal and ST EPs All-Cause Cardiac non-CV mortality type of stent thrombosis
RR072
(053-099)
P=0045
RR 075
(054-104)
P=008 1
13
06
1
0
02
04
06
08
1
12
14
Radial Femoral
P=069
P=066
Mortality Stent Thrombosis
NNTB 167
Bleeding endpoints BARC TIMI GUSTO access vs non-access related
14
25
P=0013
RR 067 049-092
P=00004
RR 037 021-066
BARC 3 or 5
P=00098
RR 064 045-090
P=008
RR 072 050-104 P=020
RR 078 053-114
Major
or minor
moderate
or severe
P=082
P=068
Rardial Better Femoral Better 1
HAZARD RATIO (95 CI)
P-VALUES
Superiority Interaction
089 Intermediate (548-991)
075 (060-094)
104 (082-132) 076 0011
Centrersquos annual
volume of PCI
Low (247-544)
Intermediate (654-790)
Centrersquos
Proportion of
radial PCI
Low (149-644)
NSTE-ACS (tpndash) ACS type
STEMI
lt75 Age
ge75 023 088 (070-109)
082 (068-097) 0023 062
NACE Subgroup Analysis
High (1000-1950)
High (800-980)
NSTE-ACS (tp+)
Men Sex
Women
lt25 BMI
ge25
No
Ticagrelor or
prasugrel Yes
No Diabetes
Yes
lt60 GFR
ge60
No
History of
PVD Yes
2 025 050
075 (058-097) 0025
00048
101 (079-129)
095 (075 -122) 071
095
064 (051-080) lt0001
044
086 (068-108)
058 (033-103) 0059
019
085 (071-102) 007
0012 072 (056-093)
089 (076-105) 016 018
009 086 (073-102)
079 (063-099) 0038 053
007 083 (068-102)
084 (070-101) 006 094
045 091 (071-117)
080 (068-094) 008 043
001 078 (065-094)
086 (070-107) 018 051
060 091 (064-130)
083 (071-096) 0012 064
Radial Better Femoral Better 1
HAZARD RATIO (95 CI)
P-VALUES
Superiority Interaction
Intermediate (654-790)
Centrersquos
Proportion
of radial PCI
Low (149-644)
NSTE-ACS (tpndash) ACS
type
STEMI
Subgroup Analysis
High (800-980)
NSTE-ACS (tp+)
2
00157
128 (071-232)
069 (040 -119) 018
041
048 (028-081) 0006
010
087 (059-129) 049
049 (028-087) 0012
Intermediate (654-790) Centrersquos
Proportion
of radial PCI
Low (149-644)
NSTE-ACS (tpndash) ACS
type
STEMI
High (800-980)
NSTE-ACS (tp+)
020
090 (054-150)
057 (031 -103) 006
068
056 (032-097) 0035
054
062 (041-094)
166 (028-100) 058
0022
070 (042-117) 017
Mortality
Bleeding
4 050 025
1 2 050 025
Updated Meta-analysis 19328 ACS patients being randomly allocated to radial or femoral access
Rardial Better Femoral Better 1 4 025 050 2
Pre-Rival RIVAL Post-RIVAL MATRI
X Combined
Non-CABG
major bleeds
Death
myocardial
infarction or
stroke
Death
Myocardial
Infarction
Stroke
Pre-Rival RIVAL Post-RIVAL MATRI
X Combined
Pre-Rival RIVAL Post-RIVAL MATRI
X Combined
Pre-Rival RIVAL Post-RIVAL MATRI
X Combined
Pre-Rival RIVAL Post-RIVAL MATRI
X Combined
SUBGROUP Risk Ratio (95CI) P Value
Heterogenity
P Value I2
073 (043-123) 039 (023-067)
058 (046-072)
041 (022-076)
lt00001 0 05
1
067 (048-093) 086 (076-098) 086 (077-095)
098 (076-127)
00051 0 09
7
058 (039-087) 073 (053-099) 072 (060-088) 00011 0 10
0
085 (039-190) 091 (078-106) 091 (079-104)
092 (065-131)
01
6 0 08
8
068 (049-092)
082 (052-129)
077 (046-128) 086 (058-129)
073 (012-447)
140 (045-440) 100 (050-200) 105 (069-160)
143 (072-283)
08
0 0 07
5
026 (006-123)
Summary bull Among patients with an ACS with or without ST-segment
elevation who underwent invasive management the use
of radial access for coronary angiography plusmn PCI reduced
the rate of net adverse clinical events with a number
needed to treat for benefit of 53
ndash Differences between groups were driven by reductions in BARC
major bleeding unrelated to CABG and all-cause mortality with
radial access
bull Our results in conjunction with the updated meta-
analysis suggest that radial approach should
become the default access for patients with
ACS undergoing invasive management
Radial Acces 61000 menos Muertes
LA VIA TRANSRADIAL DEBERIA SER EL ACCESO DE ELECCION o ldquo DEFAULTrdquo PARA LOS PACIENTES CON SCA TRATADOS CON INTERVENCIONISMO PERCUTANEO
LA VIA TRANSRADIAL DEBERIA SER EL ACCESO DE ELECCION PARA TODO PACIENTE CONSIN SCA TRATADOS CON INTERVENCIONISMO PERCUTANEO
GRACIAS POR SU ATENCION
MACE
Mortality
No interaction between access and anticoagulant use in a post- hoc analysis of the subgroup of 7213 patients randomized to bivalirudin or unfractionated heparin for the two co-primary outcomes all-cause mortality or BARC 3 or 5 bleeding
Relevance of bleeding as a clinical endpoint
bull Availability of potent antithrombotic therapy including ndash ASA ndash P2Y12 inhibitors (clopidogrel prasugrel ticagrelor) ndash heparin ndash GP IIbIIIa inhibitors ndash direct thrombin inhibitors
bull has led to a reduction in ischemic events bull but is associated with an increased risk of
bleeding bull the increase in bleeding is associated with worse
clinical outcome
Rationale for a new bleeding definition
bull Increased importance of bleeding as prognostic factor
bull Need for assessment of bleeding in RCTs and registries
bull Lack of comparability bull Need for standardized definitions to avoid
erroneous conclusions
ndash regarding safety of a given agent ndash regarding superiority of one agent over another
Open questions regarding BARC
bull Why 48-hour window for CABG-related bleeding
bull Why type 1 bdquonot actionableldquo when patient may bdquotake actionldquo such as discontinuing medication (with potentially serious consequences such as ST)
bull Why consider intraocular bleed equivalent to intracranial bleed for BARC 3c
bull Type 1 bleed subject to misinterpretation by the patient
Hicks et al (editorial) Circulation 20111232664
Conclusion
bull BARC is a new objective hierarchically graded classification of bleeding
(Mehran Circulation [June 14] 20111232736)
bull BARC is based on consensus rather than data-driven
bull Prospective validation is warranted ndash across the spectrum of IHD
ndash across management strategies (conservative invasive)
ndash in the context of all invasive procedures (PCI CABG endovascular TAVI)
Conclusion (2)
bull Final validation of BARC and proof of its utility depend on
ndash its use by all future RCTs as common safety endpoint
ndash unanimous assessment procedure (questionnaires)
bull More important than using one or the other bleeding risk score is the agreement and commitment among clinical trialists to use the same score for comparability of data
Procedimientos INCC 2014
N 1455
Acceso radial en el tratamiento intervencionista del infarto agudo de miocardio con sobreelevacioacuten del ST Dr Gabriel Pintos INCC
OBJETIVO Evaluar los resultados obtenidos en el tratamiento intervencionista de pacientes con IAMcST realizado por acceso radial
MEacuteTODO Estudio analiacutetico de cohorte
Desde el 01012003 hasta el 31122009 se trataron 2114 pacientes con IAMcST en curso (lt24 hs de evolucioacuten) Se incluyeron en la base de datos de la institucioacuten y se registroacute prospectivamente
bull Comorbilidad bull Procedimiento realizado bull Tipo y nuacutemero de arterias tratadas bull Dispositivos utilizados bull Evolucioacuten pos procedimiento inmediata
0
20
40
60
80
100
393 874 96
n꞊280 n꞊657 n꞊1177
Incidencia del acceso radial en IAMcST seguacuten eacutepoca
SUPERVIVENCIA SEGUacuteN ACCESO VASCULAR
p lt 001
diacuteas
AF 057
AR 068
CONCLUSIONES
El ACCESO RADIAL se asocioacute a disminucioacuten del riesgo de
MUERTE a corto y largo plazo en el tratamiento intervencionista
del IAMcST y por tanto PODRIA SER LA VIA DE ABORDAJE DE
ELECCION EN ESTOS PACIENTES
Adoption of Radial Access in PCI in US Trend in the Use of r-PCI Over Time in the Overall amp Key Subgroups
Feldman et al Circulation 20131272295
All Patients
Pts with Stable angina NSTE ACS STEMI
Overall Radial PCI
R
ad
ial
20
07
- Q
tr
20
07
- Q
tr
20
08
- Q
tr
20
08
- Q
tr
20
09
- Q
tr
20
09
- Q
tr
20
10
- Q
tr
20
10
- Q
tr
20
11
- Q
tr
20
11
- Q
tr
20
12
- Q
tr
20
12
- Q
tr
20
18
16
14
12
10
8
6
4
2
161
R
ad
ial
20
07
- Q
tr
20
07
- Q
tr
20
08
- Q
tr
20
08
- Q
tr
20
09
- Q
tr
20
09
- Q
tr
20
10
- Q
tr
20
10
- Q
tr
20
11
- Q
tr
20
11
- Q
tr
20
12
- Q
tr
20
12
- Q
tr
Male Female 20
18
16
14
12
10
8
6
4
2
R
ad
ial
20
07
- Q
tr
20
07
- Q
tr
20
08
- Q
tr
20
08
- Q
tr
20
09
- Q
tr
20
09
- Q
tr
20
10
- Q
tr
20
10
- Q
tr
20
11
- Q
tr
20
11
- Q
tr
20
12
- Q
tr
20
12
- Q
tr
UANSTEMI STEMI Stable Angina 2
0
1
8
1
6
1
4
1
2
1
0
8
6
4
2
IAM
bull All antithrombotic agents (except fondaparinux bivalirudin) are associated with increased bleeding risk
bull Aspirin and heparin reduce death MI at 30 days in NSTE-ACS
Choice of arterial access site and outcomes in patients with acute coronary
siacutendromes managed with an early invasive strategy the ACUITY trial Hamon M Rasmussen LH Manoukian SV Cequier A Lincoff MA Rupprecht HJ Gersh BJ Mann T Bertrand ME Mehran R Stone GW
AIMS The purpose of this study was to evaluate the impact of arterial access site on bleeding and ischaemic outcomes overall and by
treatment strategy in patients with acute coronary syndromes (ACS)
METHODS AND RESULTS In the ACUITY trial 13819 patients with moderate and high-risk ACS were randomised to either heparin
(unfractionated or enoxaparin) plus a glycoprotein IIbIIIa inhibitor (GPI) bivalirudin plus a GPI or bivalirudin alone
Per operator choice femoral access was utilised in 11989 patients (938) and radial Access in 798 patients (62) There was no significant
difference in composite ischaemia between the radial and femoral approaches at 30 days (81 vs 75 p=018) or 1 year (147 vs
155 p=077)although fewer major bleeding complications occurred with the use of radial access (30vs48 p=003) Use of
bivalirudin monotherapy was associated with significantly less 30-day major bleeding than heparin plus GPI after femoral access
(30 vs 58 plt00001) but not with radial access (42 vs 22 P=019)
Major or minor organ bleeding was reduced with bivalirudin monotherapy compared to heparin plus GPI to a similar extent with both
femoral (41 vs 74 Plt00001) and radial (49 vs 72 P=026) access
EuroIntervention 2009 May5(1)115-20
CONCLUSIONS
Transradial compared to femoral arterial access is associated with similar rates of composite ischaemia
anwith fewer major bleeding complications in patients with ACS managed invasively
Bivalirudin monotherapy compared to heparin plus GPIs significantly reduces
access site related major bleeding complications with femoral
but not radial artery access though non-access site related bleeding is reduced by
bivalirudin monotherapy in all patients
0 5 10 15 20 25 30
0
20
40
60
80
100
120
140
Mo
rta
lity
(
)
CURE=Clopidogrel in Unstable angina to prevent Recurrent ischemic Events (study) OASIS=Organization to Assess
Strategies for Ischemic Syndromes (study)
Reproduced with permission from Eikelboom JW et al Circulation 2006114774-782
Major Bleeding During First 30 Days Is Associated With Mortality Meta-analysis of 34146
ACS patients from the randomized OASIS OASIS-2 and CURE trials assessed the
association between bleeding within the first 30 days and death
Without major bleeding
With major bleeding
Days
Mo
rtality
(
)
Days from randomization
0 30 60 90 120 150 180 210 240 270 300 330 360 390
0
5
15
30
10
25
20
Major bleed only (without MI) (n=551)
Both MI and major bleed (n=94)
No MI or major bleed (n=12557)
MI only (without major bleed) (n=611)
Data on file The Medicines Company Parsippany NJ
289
125
86
34
Univariate analysis of 13819 patients from ACUITY
Impact of Non-CABG Major Bleeding and
MI at 30 Days on 1-Year Mortality
Radial Access 798 pts 62
Am Heart J 2009 Jan157(1)164-9 Epub 2008 Nov 6
Am Heart J 2009 Jan157(1)164-9 Epub 2008 Nov 6
Hypothetical mechanisms linking bleeding and mortality
Steg P G et al Eur Heart J 2011321854-
1864
Existing bleeding scores
bull TIMI Laboratory-based (hemoglobin hematocrit decrease)
bull GUSTO Clinical (severity)-based
bull GRACE Simplified laboratory and clinical
bull CURE Major minor (combined clin + lab)
bull ACUITY Major (intracranial-ocular access-site retroperit) lab
bull REPLACE-2 bull ISAR-REACT 3 bull PLATO bull STEEPLE bull CURRENT-OASIS
Thrombolysis conservative
PCI-based
BARC (Bleeding Academic Research Consortium) definitions
Mehran et al Circulation 20111232736-2747
bull Type 0 no evidence of bleeding bull Type 1 bleeding that is not actionable without
need for hospitalization or treatment (eg bruising hematoma nosebleeds etc)
bull Type 2 any clinically overt sign of hemorrhage that is actionable but does not meet criteria for type 3 4 or 5 Must meet at least 1 of following criteria ndash Requires intervention ndash Leads to hospitalization MANEJO MEDICO ndash Prompts evaluation
BARC (Bleeding Academic Research Consortium) definitions
Mehran et al Circulation 20111232736-2747
bull Type 3 clinical laboratory andor imaging evidence of bleeding with healthcare provider responses ndash BARC type 3a
bull any transfusion with overt bleeding bull overt bleeding plus hemoglobin drop ge3 to lt5 gdL
ndash BARC type 3b bull overt bleeding plus hemoglobin drop gt5 gdL bull Cardiac tamponade bull Bleeding requiring surgical intervention for control (excluding dentalnasalskinhemorrhoid) bull Bleeding requiring intravenous vasoactive drugs
ndash BARC type 3c bull Intracranial hemorrhage subcategories confirmed by autopsy
imaging or lumbar puncture bull Intraocular bleed compromising vision
BARC Bleeding Academic Research Consortium) definitions
Mehran et al Circulation 20111232736-2747
bull Type 4 Coronary Artery Bypass Graftndashrelated bleeding ndash Perioperative intracranial bleeding within 48 hours ndash Reoperation after closure of sternotomy for the purpose of controlling bleeding ndash Transfusion of ge5 U whole blood or packed red blood cells within a 48-hour period ndash Chest tube output 2 L within a 24-hour period
bull Type 5 ndash fatal bleeding bull Probable fatal bleeding (type 5a)
ndash bleeding that is clinically suspicious as the cause of death but the bleeding is not directly observed and there is no autopsy or confirmatory imaging
bull Definite fatal bleeding (type 5b) ndash bleeding that is directly observed (by either clinical specimen [blood
emesis stool etc] or imaging) or confirmed on autopsy
26 VCD
11
NSTEACS or STEMI with invasive management Aspirin+P2Y12 blocker
Trans-Femoral Access
Trans-Radial Access
To demonstrate that trans-radial intervention as
compared to femoral access site is associated to lower
rate of the composite endpoint of Death MI or Stroke
within the first 30 days
1deg co-Primary Objective
6 vs 42 βlt10 α 25 8200 patients
Adaptive study Design sample size (SS) will be increased
by the cross-over rate at 70 of planned SS
MATRIX Access site NCT01433627
MATRIX Access
39 93 132 200 276 380 490 685 857 1002 1190
1400 1684 1972 2248
2584 2926
3256 3560
3875 4144
4452 4726
5000 5322
5655 5896 6184
6458 6742 6982 7235 7444 7638 7844 8073
8404
Cumulative enrollment by month
8404
8404
8404 patients with ACS undergoing coronary angiography plusmn PCI from 11th Oct 2011 to 7th Nov 2014
Operator Eligibility Criteria Interventional cardiologist expertise in TRI and TFI including at least 75 transradial coronary interventions and at least 50 of interventions performed via radial route in the year preceding site initiation
Complete follow-up to 30 days available in 4183 (997) of radial and 4191 (99middot6) of femoral cohorts
Am Heart J 2014 Dec168(6)838-45e6
Cross Over and Procedural Success Rates
941 of radial and 974 of femoral cohorts received respective treatment as allocated
In 58 of radial and 23 of TF cohort the allocated access was attempted but failed
In 3 (01) in the radial and 13 (03) patients in the femoral groups the allocated access was not attempted
P=077 Plt0001
TIMI lt3 andor final stenosis gt30
88
103
15 significant reduction at nominal 5 alpha
which is however NOT significant at the pre-specificed
alpha of 25
Primary EP MACE
Femoral
Radial
Rate Ratio 083 95 CI 073 to 096 p=00092
117
98
NNTB 53 Femoral
Radial
Primary EP NACE
Mortalidad Total
IAM
Fatal and ST EPs All-Cause Cardiac non-CV mortality type of stent thrombosis
RR072
(053-099)
P=0045
RR 075
(054-104)
P=008 1
13
06
1
0
02
04
06
08
1
12
14
Radial Femoral
P=069
P=066
Mortality Stent Thrombosis
NNTB 167
Bleeding endpoints BARC TIMI GUSTO access vs non-access related
14
25
P=0013
RR 067 049-092
P=00004
RR 037 021-066
BARC 3 or 5
P=00098
RR 064 045-090
P=008
RR 072 050-104 P=020
RR 078 053-114
Major
or minor
moderate
or severe
P=082
P=068
Rardial Better Femoral Better 1
HAZARD RATIO (95 CI)
P-VALUES
Superiority Interaction
089 Intermediate (548-991)
075 (060-094)
104 (082-132) 076 0011
Centrersquos annual
volume of PCI
Low (247-544)
Intermediate (654-790)
Centrersquos
Proportion of
radial PCI
Low (149-644)
NSTE-ACS (tpndash) ACS type
STEMI
lt75 Age
ge75 023 088 (070-109)
082 (068-097) 0023 062
NACE Subgroup Analysis
High (1000-1950)
High (800-980)
NSTE-ACS (tp+)
Men Sex
Women
lt25 BMI
ge25
No
Ticagrelor or
prasugrel Yes
No Diabetes
Yes
lt60 GFR
ge60
No
History of
PVD Yes
2 025 050
075 (058-097) 0025
00048
101 (079-129)
095 (075 -122) 071
095
064 (051-080) lt0001
044
086 (068-108)
058 (033-103) 0059
019
085 (071-102) 007
0012 072 (056-093)
089 (076-105) 016 018
009 086 (073-102)
079 (063-099) 0038 053
007 083 (068-102)
084 (070-101) 006 094
045 091 (071-117)
080 (068-094) 008 043
001 078 (065-094)
086 (070-107) 018 051
060 091 (064-130)
083 (071-096) 0012 064
Radial Better Femoral Better 1
HAZARD RATIO (95 CI)
P-VALUES
Superiority Interaction
Intermediate (654-790)
Centrersquos
Proportion
of radial PCI
Low (149-644)
NSTE-ACS (tpndash) ACS
type
STEMI
Subgroup Analysis
High (800-980)
NSTE-ACS (tp+)
2
00157
128 (071-232)
069 (040 -119) 018
041
048 (028-081) 0006
010
087 (059-129) 049
049 (028-087) 0012
Intermediate (654-790) Centrersquos
Proportion
of radial PCI
Low (149-644)
NSTE-ACS (tpndash) ACS
type
STEMI
High (800-980)
NSTE-ACS (tp+)
020
090 (054-150)
057 (031 -103) 006
068
056 (032-097) 0035
054
062 (041-094)
166 (028-100) 058
0022
070 (042-117) 017
Mortality
Bleeding
4 050 025
1 2 050 025
Updated Meta-analysis 19328 ACS patients being randomly allocated to radial or femoral access
Rardial Better Femoral Better 1 4 025 050 2
Pre-Rival RIVAL Post-RIVAL MATRI
X Combined
Non-CABG
major bleeds
Death
myocardial
infarction or
stroke
Death
Myocardial
Infarction
Stroke
Pre-Rival RIVAL Post-RIVAL MATRI
X Combined
Pre-Rival RIVAL Post-RIVAL MATRI
X Combined
Pre-Rival RIVAL Post-RIVAL MATRI
X Combined
Pre-Rival RIVAL Post-RIVAL MATRI
X Combined
SUBGROUP Risk Ratio (95CI) P Value
Heterogenity
P Value I2
073 (043-123) 039 (023-067)
058 (046-072)
041 (022-076)
lt00001 0 05
1
067 (048-093) 086 (076-098) 086 (077-095)
098 (076-127)
00051 0 09
7
058 (039-087) 073 (053-099) 072 (060-088) 00011 0 10
0
085 (039-190) 091 (078-106) 091 (079-104)
092 (065-131)
01
6 0 08
8
068 (049-092)
082 (052-129)
077 (046-128) 086 (058-129)
073 (012-447)
140 (045-440) 100 (050-200) 105 (069-160)
143 (072-283)
08
0 0 07
5
026 (006-123)
Summary bull Among patients with an ACS with or without ST-segment
elevation who underwent invasive management the use
of radial access for coronary angiography plusmn PCI reduced
the rate of net adverse clinical events with a number
needed to treat for benefit of 53
ndash Differences between groups were driven by reductions in BARC
major bleeding unrelated to CABG and all-cause mortality with
radial access
bull Our results in conjunction with the updated meta-
analysis suggest that radial approach should
become the default access for patients with
ACS undergoing invasive management
Radial Acces 61000 menos Muertes
LA VIA TRANSRADIAL DEBERIA SER EL ACCESO DE ELECCION o ldquo DEFAULTrdquo PARA LOS PACIENTES CON SCA TRATADOS CON INTERVENCIONISMO PERCUTANEO
LA VIA TRANSRADIAL DEBERIA SER EL ACCESO DE ELECCION PARA TODO PACIENTE CONSIN SCA TRATADOS CON INTERVENCIONISMO PERCUTANEO
GRACIAS POR SU ATENCION
MACE
Mortality
No interaction between access and anticoagulant use in a post- hoc analysis of the subgroup of 7213 patients randomized to bivalirudin or unfractionated heparin for the two co-primary outcomes all-cause mortality or BARC 3 or 5 bleeding
Relevance of bleeding as a clinical endpoint
bull Availability of potent antithrombotic therapy including ndash ASA ndash P2Y12 inhibitors (clopidogrel prasugrel ticagrelor) ndash heparin ndash GP IIbIIIa inhibitors ndash direct thrombin inhibitors
bull has led to a reduction in ischemic events bull but is associated with an increased risk of
bleeding bull the increase in bleeding is associated with worse
clinical outcome
Rationale for a new bleeding definition
bull Increased importance of bleeding as prognostic factor
bull Need for assessment of bleeding in RCTs and registries
bull Lack of comparability bull Need for standardized definitions to avoid
erroneous conclusions
ndash regarding safety of a given agent ndash regarding superiority of one agent over another
Open questions regarding BARC
bull Why 48-hour window for CABG-related bleeding
bull Why type 1 bdquonot actionableldquo when patient may bdquotake actionldquo such as discontinuing medication (with potentially serious consequences such as ST)
bull Why consider intraocular bleed equivalent to intracranial bleed for BARC 3c
bull Type 1 bleed subject to misinterpretation by the patient
Hicks et al (editorial) Circulation 20111232664
Conclusion
bull BARC is a new objective hierarchically graded classification of bleeding
(Mehran Circulation [June 14] 20111232736)
bull BARC is based on consensus rather than data-driven
bull Prospective validation is warranted ndash across the spectrum of IHD
ndash across management strategies (conservative invasive)
ndash in the context of all invasive procedures (PCI CABG endovascular TAVI)
Conclusion (2)
bull Final validation of BARC and proof of its utility depend on
ndash its use by all future RCTs as common safety endpoint
ndash unanimous assessment procedure (questionnaires)
bull More important than using one or the other bleeding risk score is the agreement and commitment among clinical trialists to use the same score for comparability of data
Acceso radial en el tratamiento intervencionista del infarto agudo de miocardio con sobreelevacioacuten del ST Dr Gabriel Pintos INCC
OBJETIVO Evaluar los resultados obtenidos en el tratamiento intervencionista de pacientes con IAMcST realizado por acceso radial
MEacuteTODO Estudio analiacutetico de cohorte
Desde el 01012003 hasta el 31122009 se trataron 2114 pacientes con IAMcST en curso (lt24 hs de evolucioacuten) Se incluyeron en la base de datos de la institucioacuten y se registroacute prospectivamente
bull Comorbilidad bull Procedimiento realizado bull Tipo y nuacutemero de arterias tratadas bull Dispositivos utilizados bull Evolucioacuten pos procedimiento inmediata
0
20
40
60
80
100
393 874 96
n꞊280 n꞊657 n꞊1177
Incidencia del acceso radial en IAMcST seguacuten eacutepoca
SUPERVIVENCIA SEGUacuteN ACCESO VASCULAR
p lt 001
diacuteas
AF 057
AR 068
CONCLUSIONES
El ACCESO RADIAL se asocioacute a disminucioacuten del riesgo de
MUERTE a corto y largo plazo en el tratamiento intervencionista
del IAMcST y por tanto PODRIA SER LA VIA DE ABORDAJE DE
ELECCION EN ESTOS PACIENTES
Adoption of Radial Access in PCI in US Trend in the Use of r-PCI Over Time in the Overall amp Key Subgroups
Feldman et al Circulation 20131272295
All Patients
Pts with Stable angina NSTE ACS STEMI
Overall Radial PCI
R
ad
ial
20
07
- Q
tr
20
07
- Q
tr
20
08
- Q
tr
20
08
- Q
tr
20
09
- Q
tr
20
09
- Q
tr
20
10
- Q
tr
20
10
- Q
tr
20
11
- Q
tr
20
11
- Q
tr
20
12
- Q
tr
20
12
- Q
tr
20
18
16
14
12
10
8
6
4
2
161
R
ad
ial
20
07
- Q
tr
20
07
- Q
tr
20
08
- Q
tr
20
08
- Q
tr
20
09
- Q
tr
20
09
- Q
tr
20
10
- Q
tr
20
10
- Q
tr
20
11
- Q
tr
20
11
- Q
tr
20
12
- Q
tr
20
12
- Q
tr
Male Female 20
18
16
14
12
10
8
6
4
2
R
ad
ial
20
07
- Q
tr
20
07
- Q
tr
20
08
- Q
tr
20
08
- Q
tr
20
09
- Q
tr
20
09
- Q
tr
20
10
- Q
tr
20
10
- Q
tr
20
11
- Q
tr
20
11
- Q
tr
20
12
- Q
tr
20
12
- Q
tr
UANSTEMI STEMI Stable Angina 2
0
1
8
1
6
1
4
1
2
1
0
8
6
4
2
IAM
bull All antithrombotic agents (except fondaparinux bivalirudin) are associated with increased bleeding risk
bull Aspirin and heparin reduce death MI at 30 days in NSTE-ACS
Choice of arterial access site and outcomes in patients with acute coronary
siacutendromes managed with an early invasive strategy the ACUITY trial Hamon M Rasmussen LH Manoukian SV Cequier A Lincoff MA Rupprecht HJ Gersh BJ Mann T Bertrand ME Mehran R Stone GW
AIMS The purpose of this study was to evaluate the impact of arterial access site on bleeding and ischaemic outcomes overall and by
treatment strategy in patients with acute coronary syndromes (ACS)
METHODS AND RESULTS In the ACUITY trial 13819 patients with moderate and high-risk ACS were randomised to either heparin
(unfractionated or enoxaparin) plus a glycoprotein IIbIIIa inhibitor (GPI) bivalirudin plus a GPI or bivalirudin alone
Per operator choice femoral access was utilised in 11989 patients (938) and radial Access in 798 patients (62) There was no significant
difference in composite ischaemia between the radial and femoral approaches at 30 days (81 vs 75 p=018) or 1 year (147 vs
155 p=077)although fewer major bleeding complications occurred with the use of radial access (30vs48 p=003) Use of
bivalirudin monotherapy was associated with significantly less 30-day major bleeding than heparin plus GPI after femoral access
(30 vs 58 plt00001) but not with radial access (42 vs 22 P=019)
Major or minor organ bleeding was reduced with bivalirudin monotherapy compared to heparin plus GPI to a similar extent with both
femoral (41 vs 74 Plt00001) and radial (49 vs 72 P=026) access
EuroIntervention 2009 May5(1)115-20
CONCLUSIONS
Transradial compared to femoral arterial access is associated with similar rates of composite ischaemia
anwith fewer major bleeding complications in patients with ACS managed invasively
Bivalirudin monotherapy compared to heparin plus GPIs significantly reduces
access site related major bleeding complications with femoral
but not radial artery access though non-access site related bleeding is reduced by
bivalirudin monotherapy in all patients
0 5 10 15 20 25 30
0
20
40
60
80
100
120
140
Mo
rta
lity
(
)
CURE=Clopidogrel in Unstable angina to prevent Recurrent ischemic Events (study) OASIS=Organization to Assess
Strategies for Ischemic Syndromes (study)
Reproduced with permission from Eikelboom JW et al Circulation 2006114774-782
Major Bleeding During First 30 Days Is Associated With Mortality Meta-analysis of 34146
ACS patients from the randomized OASIS OASIS-2 and CURE trials assessed the
association between bleeding within the first 30 days and death
Without major bleeding
With major bleeding
Days
Mo
rtality
(
)
Days from randomization
0 30 60 90 120 150 180 210 240 270 300 330 360 390
0
5
15
30
10
25
20
Major bleed only (without MI) (n=551)
Both MI and major bleed (n=94)
No MI or major bleed (n=12557)
MI only (without major bleed) (n=611)
Data on file The Medicines Company Parsippany NJ
289
125
86
34
Univariate analysis of 13819 patients from ACUITY
Impact of Non-CABG Major Bleeding and
MI at 30 Days on 1-Year Mortality
Radial Access 798 pts 62
Am Heart J 2009 Jan157(1)164-9 Epub 2008 Nov 6
Am Heart J 2009 Jan157(1)164-9 Epub 2008 Nov 6
Hypothetical mechanisms linking bleeding and mortality
Steg P G et al Eur Heart J 2011321854-
1864
Existing bleeding scores
bull TIMI Laboratory-based (hemoglobin hematocrit decrease)
bull GUSTO Clinical (severity)-based
bull GRACE Simplified laboratory and clinical
bull CURE Major minor (combined clin + lab)
bull ACUITY Major (intracranial-ocular access-site retroperit) lab
bull REPLACE-2 bull ISAR-REACT 3 bull PLATO bull STEEPLE bull CURRENT-OASIS
Thrombolysis conservative
PCI-based
BARC (Bleeding Academic Research Consortium) definitions
Mehran et al Circulation 20111232736-2747
bull Type 0 no evidence of bleeding bull Type 1 bleeding that is not actionable without
need for hospitalization or treatment (eg bruising hematoma nosebleeds etc)
bull Type 2 any clinically overt sign of hemorrhage that is actionable but does not meet criteria for type 3 4 or 5 Must meet at least 1 of following criteria ndash Requires intervention ndash Leads to hospitalization MANEJO MEDICO ndash Prompts evaluation
BARC (Bleeding Academic Research Consortium) definitions
Mehran et al Circulation 20111232736-2747
bull Type 3 clinical laboratory andor imaging evidence of bleeding with healthcare provider responses ndash BARC type 3a
bull any transfusion with overt bleeding bull overt bleeding plus hemoglobin drop ge3 to lt5 gdL
ndash BARC type 3b bull overt bleeding plus hemoglobin drop gt5 gdL bull Cardiac tamponade bull Bleeding requiring surgical intervention for control (excluding dentalnasalskinhemorrhoid) bull Bleeding requiring intravenous vasoactive drugs
ndash BARC type 3c bull Intracranial hemorrhage subcategories confirmed by autopsy
imaging or lumbar puncture bull Intraocular bleed compromising vision
BARC Bleeding Academic Research Consortium) definitions
Mehran et al Circulation 20111232736-2747
bull Type 4 Coronary Artery Bypass Graftndashrelated bleeding ndash Perioperative intracranial bleeding within 48 hours ndash Reoperation after closure of sternotomy for the purpose of controlling bleeding ndash Transfusion of ge5 U whole blood or packed red blood cells within a 48-hour period ndash Chest tube output 2 L within a 24-hour period
bull Type 5 ndash fatal bleeding bull Probable fatal bleeding (type 5a)
ndash bleeding that is clinically suspicious as the cause of death but the bleeding is not directly observed and there is no autopsy or confirmatory imaging
bull Definite fatal bleeding (type 5b) ndash bleeding that is directly observed (by either clinical specimen [blood
emesis stool etc] or imaging) or confirmed on autopsy
26 VCD
11
NSTEACS or STEMI with invasive management Aspirin+P2Y12 blocker
Trans-Femoral Access
Trans-Radial Access
To demonstrate that trans-radial intervention as
compared to femoral access site is associated to lower
rate of the composite endpoint of Death MI or Stroke
within the first 30 days
1deg co-Primary Objective
6 vs 42 βlt10 α 25 8200 patients
Adaptive study Design sample size (SS) will be increased
by the cross-over rate at 70 of planned SS
MATRIX Access site NCT01433627
MATRIX Access
39 93 132 200 276 380 490 685 857 1002 1190
1400 1684 1972 2248
2584 2926
3256 3560
3875 4144
4452 4726
5000 5322
5655 5896 6184
6458 6742 6982 7235 7444 7638 7844 8073
8404
Cumulative enrollment by month
8404
8404
8404 patients with ACS undergoing coronary angiography plusmn PCI from 11th Oct 2011 to 7th Nov 2014
Operator Eligibility Criteria Interventional cardiologist expertise in TRI and TFI including at least 75 transradial coronary interventions and at least 50 of interventions performed via radial route in the year preceding site initiation
Complete follow-up to 30 days available in 4183 (997) of radial and 4191 (99middot6) of femoral cohorts
Am Heart J 2014 Dec168(6)838-45e6
Cross Over and Procedural Success Rates
941 of radial and 974 of femoral cohorts received respective treatment as allocated
In 58 of radial and 23 of TF cohort the allocated access was attempted but failed
In 3 (01) in the radial and 13 (03) patients in the femoral groups the allocated access was not attempted
P=077 Plt0001
TIMI lt3 andor final stenosis gt30
88
103
15 significant reduction at nominal 5 alpha
which is however NOT significant at the pre-specificed
alpha of 25
Primary EP MACE
Femoral
Radial
Rate Ratio 083 95 CI 073 to 096 p=00092
117
98
NNTB 53 Femoral
Radial
Primary EP NACE
Mortalidad Total
IAM
Fatal and ST EPs All-Cause Cardiac non-CV mortality type of stent thrombosis
RR072
(053-099)
P=0045
RR 075
(054-104)
P=008 1
13
06
1
0
02
04
06
08
1
12
14
Radial Femoral
P=069
P=066
Mortality Stent Thrombosis
NNTB 167
Bleeding endpoints BARC TIMI GUSTO access vs non-access related
14
25
P=0013
RR 067 049-092
P=00004
RR 037 021-066
BARC 3 or 5
P=00098
RR 064 045-090
P=008
RR 072 050-104 P=020
RR 078 053-114
Major
or minor
moderate
or severe
P=082
P=068
Rardial Better Femoral Better 1
HAZARD RATIO (95 CI)
P-VALUES
Superiority Interaction
089 Intermediate (548-991)
075 (060-094)
104 (082-132) 076 0011
Centrersquos annual
volume of PCI
Low (247-544)
Intermediate (654-790)
Centrersquos
Proportion of
radial PCI
Low (149-644)
NSTE-ACS (tpndash) ACS type
STEMI
lt75 Age
ge75 023 088 (070-109)
082 (068-097) 0023 062
NACE Subgroup Analysis
High (1000-1950)
High (800-980)
NSTE-ACS (tp+)
Men Sex
Women
lt25 BMI
ge25
No
Ticagrelor or
prasugrel Yes
No Diabetes
Yes
lt60 GFR
ge60
No
History of
PVD Yes
2 025 050
075 (058-097) 0025
00048
101 (079-129)
095 (075 -122) 071
095
064 (051-080) lt0001
044
086 (068-108)
058 (033-103) 0059
019
085 (071-102) 007
0012 072 (056-093)
089 (076-105) 016 018
009 086 (073-102)
079 (063-099) 0038 053
007 083 (068-102)
084 (070-101) 006 094
045 091 (071-117)
080 (068-094) 008 043
001 078 (065-094)
086 (070-107) 018 051
060 091 (064-130)
083 (071-096) 0012 064
Radial Better Femoral Better 1
HAZARD RATIO (95 CI)
P-VALUES
Superiority Interaction
Intermediate (654-790)
Centrersquos
Proportion
of radial PCI
Low (149-644)
NSTE-ACS (tpndash) ACS
type
STEMI
Subgroup Analysis
High (800-980)
NSTE-ACS (tp+)
2
00157
128 (071-232)
069 (040 -119) 018
041
048 (028-081) 0006
010
087 (059-129) 049
049 (028-087) 0012
Intermediate (654-790) Centrersquos
Proportion
of radial PCI
Low (149-644)
NSTE-ACS (tpndash) ACS
type
STEMI
High (800-980)
NSTE-ACS (tp+)
020
090 (054-150)
057 (031 -103) 006
068
056 (032-097) 0035
054
062 (041-094)
166 (028-100) 058
0022
070 (042-117) 017
Mortality
Bleeding
4 050 025
1 2 050 025
Updated Meta-analysis 19328 ACS patients being randomly allocated to radial or femoral access
Rardial Better Femoral Better 1 4 025 050 2
Pre-Rival RIVAL Post-RIVAL MATRI
X Combined
Non-CABG
major bleeds
Death
myocardial
infarction or
stroke
Death
Myocardial
Infarction
Stroke
Pre-Rival RIVAL Post-RIVAL MATRI
X Combined
Pre-Rival RIVAL Post-RIVAL MATRI
X Combined
Pre-Rival RIVAL Post-RIVAL MATRI
X Combined
Pre-Rival RIVAL Post-RIVAL MATRI
X Combined
SUBGROUP Risk Ratio (95CI) P Value
Heterogenity
P Value I2
073 (043-123) 039 (023-067)
058 (046-072)
041 (022-076)
lt00001 0 05
1
067 (048-093) 086 (076-098) 086 (077-095)
098 (076-127)
00051 0 09
7
058 (039-087) 073 (053-099) 072 (060-088) 00011 0 10
0
085 (039-190) 091 (078-106) 091 (079-104)
092 (065-131)
01
6 0 08
8
068 (049-092)
082 (052-129)
077 (046-128) 086 (058-129)
073 (012-447)
140 (045-440) 100 (050-200) 105 (069-160)
143 (072-283)
08
0 0 07
5
026 (006-123)
Summary bull Among patients with an ACS with or without ST-segment
elevation who underwent invasive management the use
of radial access for coronary angiography plusmn PCI reduced
the rate of net adverse clinical events with a number
needed to treat for benefit of 53
ndash Differences between groups were driven by reductions in BARC
major bleeding unrelated to CABG and all-cause mortality with
radial access
bull Our results in conjunction with the updated meta-
analysis suggest that radial approach should
become the default access for patients with
ACS undergoing invasive management
Radial Acces 61000 menos Muertes
LA VIA TRANSRADIAL DEBERIA SER EL ACCESO DE ELECCION o ldquo DEFAULTrdquo PARA LOS PACIENTES CON SCA TRATADOS CON INTERVENCIONISMO PERCUTANEO
LA VIA TRANSRADIAL DEBERIA SER EL ACCESO DE ELECCION PARA TODO PACIENTE CONSIN SCA TRATADOS CON INTERVENCIONISMO PERCUTANEO
GRACIAS POR SU ATENCION
MACE
Mortality
No interaction between access and anticoagulant use in a post- hoc analysis of the subgroup of 7213 patients randomized to bivalirudin or unfractionated heparin for the two co-primary outcomes all-cause mortality or BARC 3 or 5 bleeding
Relevance of bleeding as a clinical endpoint
bull Availability of potent antithrombotic therapy including ndash ASA ndash P2Y12 inhibitors (clopidogrel prasugrel ticagrelor) ndash heparin ndash GP IIbIIIa inhibitors ndash direct thrombin inhibitors
bull has led to a reduction in ischemic events bull but is associated with an increased risk of
bleeding bull the increase in bleeding is associated with worse
clinical outcome
Rationale for a new bleeding definition
bull Increased importance of bleeding as prognostic factor
bull Need for assessment of bleeding in RCTs and registries
bull Lack of comparability bull Need for standardized definitions to avoid
erroneous conclusions
ndash regarding safety of a given agent ndash regarding superiority of one agent over another
Open questions regarding BARC
bull Why 48-hour window for CABG-related bleeding
bull Why type 1 bdquonot actionableldquo when patient may bdquotake actionldquo such as discontinuing medication (with potentially serious consequences such as ST)
bull Why consider intraocular bleed equivalent to intracranial bleed for BARC 3c
bull Type 1 bleed subject to misinterpretation by the patient
Hicks et al (editorial) Circulation 20111232664
Conclusion
bull BARC is a new objective hierarchically graded classification of bleeding
(Mehran Circulation [June 14] 20111232736)
bull BARC is based on consensus rather than data-driven
bull Prospective validation is warranted ndash across the spectrum of IHD
ndash across management strategies (conservative invasive)
ndash in the context of all invasive procedures (PCI CABG endovascular TAVI)
Conclusion (2)
bull Final validation of BARC and proof of its utility depend on
ndash its use by all future RCTs as common safety endpoint
ndash unanimous assessment procedure (questionnaires)
bull More important than using one or the other bleeding risk score is the agreement and commitment among clinical trialists to use the same score for comparability of data
0
20
40
60
80
100
393 874 96
n꞊280 n꞊657 n꞊1177
Incidencia del acceso radial en IAMcST seguacuten eacutepoca
SUPERVIVENCIA SEGUacuteN ACCESO VASCULAR
p lt 001
diacuteas
AF 057
AR 068
CONCLUSIONES
El ACCESO RADIAL se asocioacute a disminucioacuten del riesgo de
MUERTE a corto y largo plazo en el tratamiento intervencionista
del IAMcST y por tanto PODRIA SER LA VIA DE ABORDAJE DE
ELECCION EN ESTOS PACIENTES
Adoption of Radial Access in PCI in US Trend in the Use of r-PCI Over Time in the Overall amp Key Subgroups
Feldman et al Circulation 20131272295
All Patients
Pts with Stable angina NSTE ACS STEMI
Overall Radial PCI
R
ad
ial
20
07
- Q
tr
20
07
- Q
tr
20
08
- Q
tr
20
08
- Q
tr
20
09
- Q
tr
20
09
- Q
tr
20
10
- Q
tr
20
10
- Q
tr
20
11
- Q
tr
20
11
- Q
tr
20
12
- Q
tr
20
12
- Q
tr
20
18
16
14
12
10
8
6
4
2
161
R
ad
ial
20
07
- Q
tr
20
07
- Q
tr
20
08
- Q
tr
20
08
- Q
tr
20
09
- Q
tr
20
09
- Q
tr
20
10
- Q
tr
20
10
- Q
tr
20
11
- Q
tr
20
11
- Q
tr
20
12
- Q
tr
20
12
- Q
tr
Male Female 20
18
16
14
12
10
8
6
4
2
R
ad
ial
20
07
- Q
tr
20
07
- Q
tr
20
08
- Q
tr
20
08
- Q
tr
20
09
- Q
tr
20
09
- Q
tr
20
10
- Q
tr
20
10
- Q
tr
20
11
- Q
tr
20
11
- Q
tr
20
12
- Q
tr
20
12
- Q
tr
UANSTEMI STEMI Stable Angina 2
0
1
8
1
6
1
4
1
2
1
0
8
6
4
2
IAM
bull All antithrombotic agents (except fondaparinux bivalirudin) are associated with increased bleeding risk
bull Aspirin and heparin reduce death MI at 30 days in NSTE-ACS
Choice of arterial access site and outcomes in patients with acute coronary
siacutendromes managed with an early invasive strategy the ACUITY trial Hamon M Rasmussen LH Manoukian SV Cequier A Lincoff MA Rupprecht HJ Gersh BJ Mann T Bertrand ME Mehran R Stone GW
AIMS The purpose of this study was to evaluate the impact of arterial access site on bleeding and ischaemic outcomes overall and by
treatment strategy in patients with acute coronary syndromes (ACS)
METHODS AND RESULTS In the ACUITY trial 13819 patients with moderate and high-risk ACS were randomised to either heparin
(unfractionated or enoxaparin) plus a glycoprotein IIbIIIa inhibitor (GPI) bivalirudin plus a GPI or bivalirudin alone
Per operator choice femoral access was utilised in 11989 patients (938) and radial Access in 798 patients (62) There was no significant
difference in composite ischaemia between the radial and femoral approaches at 30 days (81 vs 75 p=018) or 1 year (147 vs
155 p=077)although fewer major bleeding complications occurred with the use of radial access (30vs48 p=003) Use of
bivalirudin monotherapy was associated with significantly less 30-day major bleeding than heparin plus GPI after femoral access
(30 vs 58 plt00001) but not with radial access (42 vs 22 P=019)
Major or minor organ bleeding was reduced with bivalirudin monotherapy compared to heparin plus GPI to a similar extent with both
femoral (41 vs 74 Plt00001) and radial (49 vs 72 P=026) access
EuroIntervention 2009 May5(1)115-20
CONCLUSIONS
Transradial compared to femoral arterial access is associated with similar rates of composite ischaemia
anwith fewer major bleeding complications in patients with ACS managed invasively
Bivalirudin monotherapy compared to heparin plus GPIs significantly reduces
access site related major bleeding complications with femoral
but not radial artery access though non-access site related bleeding is reduced by
bivalirudin monotherapy in all patients
0 5 10 15 20 25 30
0
20
40
60
80
100
120
140
Mo
rta
lity
(
)
CURE=Clopidogrel in Unstable angina to prevent Recurrent ischemic Events (study) OASIS=Organization to Assess
Strategies for Ischemic Syndromes (study)
Reproduced with permission from Eikelboom JW et al Circulation 2006114774-782
Major Bleeding During First 30 Days Is Associated With Mortality Meta-analysis of 34146
ACS patients from the randomized OASIS OASIS-2 and CURE trials assessed the
association between bleeding within the first 30 days and death
Without major bleeding
With major bleeding
Days
Mo
rtality
(
)
Days from randomization
0 30 60 90 120 150 180 210 240 270 300 330 360 390
0
5
15
30
10
25
20
Major bleed only (without MI) (n=551)
Both MI and major bleed (n=94)
No MI or major bleed (n=12557)
MI only (without major bleed) (n=611)
Data on file The Medicines Company Parsippany NJ
289
125
86
34
Univariate analysis of 13819 patients from ACUITY
Impact of Non-CABG Major Bleeding and
MI at 30 Days on 1-Year Mortality
Radial Access 798 pts 62
Am Heart J 2009 Jan157(1)164-9 Epub 2008 Nov 6
Am Heart J 2009 Jan157(1)164-9 Epub 2008 Nov 6
Hypothetical mechanisms linking bleeding and mortality
Steg P G et al Eur Heart J 2011321854-
1864
Existing bleeding scores
bull TIMI Laboratory-based (hemoglobin hematocrit decrease)
bull GUSTO Clinical (severity)-based
bull GRACE Simplified laboratory and clinical
bull CURE Major minor (combined clin + lab)
bull ACUITY Major (intracranial-ocular access-site retroperit) lab
bull REPLACE-2 bull ISAR-REACT 3 bull PLATO bull STEEPLE bull CURRENT-OASIS
Thrombolysis conservative
PCI-based
BARC (Bleeding Academic Research Consortium) definitions
Mehran et al Circulation 20111232736-2747
bull Type 0 no evidence of bleeding bull Type 1 bleeding that is not actionable without
need for hospitalization or treatment (eg bruising hematoma nosebleeds etc)
bull Type 2 any clinically overt sign of hemorrhage that is actionable but does not meet criteria for type 3 4 or 5 Must meet at least 1 of following criteria ndash Requires intervention ndash Leads to hospitalization MANEJO MEDICO ndash Prompts evaluation
BARC (Bleeding Academic Research Consortium) definitions
Mehran et al Circulation 20111232736-2747
bull Type 3 clinical laboratory andor imaging evidence of bleeding with healthcare provider responses ndash BARC type 3a
bull any transfusion with overt bleeding bull overt bleeding plus hemoglobin drop ge3 to lt5 gdL
ndash BARC type 3b bull overt bleeding plus hemoglobin drop gt5 gdL bull Cardiac tamponade bull Bleeding requiring surgical intervention for control (excluding dentalnasalskinhemorrhoid) bull Bleeding requiring intravenous vasoactive drugs
ndash BARC type 3c bull Intracranial hemorrhage subcategories confirmed by autopsy
imaging or lumbar puncture bull Intraocular bleed compromising vision
BARC Bleeding Academic Research Consortium) definitions
Mehran et al Circulation 20111232736-2747
bull Type 4 Coronary Artery Bypass Graftndashrelated bleeding ndash Perioperative intracranial bleeding within 48 hours ndash Reoperation after closure of sternotomy for the purpose of controlling bleeding ndash Transfusion of ge5 U whole blood or packed red blood cells within a 48-hour period ndash Chest tube output 2 L within a 24-hour period
bull Type 5 ndash fatal bleeding bull Probable fatal bleeding (type 5a)
ndash bleeding that is clinically suspicious as the cause of death but the bleeding is not directly observed and there is no autopsy or confirmatory imaging
bull Definite fatal bleeding (type 5b) ndash bleeding that is directly observed (by either clinical specimen [blood
emesis stool etc] or imaging) or confirmed on autopsy
26 VCD
11
NSTEACS or STEMI with invasive management Aspirin+P2Y12 blocker
Trans-Femoral Access
Trans-Radial Access
To demonstrate that trans-radial intervention as
compared to femoral access site is associated to lower
rate of the composite endpoint of Death MI or Stroke
within the first 30 days
1deg co-Primary Objective
6 vs 42 βlt10 α 25 8200 patients
Adaptive study Design sample size (SS) will be increased
by the cross-over rate at 70 of planned SS
MATRIX Access site NCT01433627
MATRIX Access
39 93 132 200 276 380 490 685 857 1002 1190
1400 1684 1972 2248
2584 2926
3256 3560
3875 4144
4452 4726
5000 5322
5655 5896 6184
6458 6742 6982 7235 7444 7638 7844 8073
8404
Cumulative enrollment by month
8404
8404
8404 patients with ACS undergoing coronary angiography plusmn PCI from 11th Oct 2011 to 7th Nov 2014
Operator Eligibility Criteria Interventional cardiologist expertise in TRI and TFI including at least 75 transradial coronary interventions and at least 50 of interventions performed via radial route in the year preceding site initiation
Complete follow-up to 30 days available in 4183 (997) of radial and 4191 (99middot6) of femoral cohorts
Am Heart J 2014 Dec168(6)838-45e6
Cross Over and Procedural Success Rates
941 of radial and 974 of femoral cohorts received respective treatment as allocated
In 58 of radial and 23 of TF cohort the allocated access was attempted but failed
In 3 (01) in the radial and 13 (03) patients in the femoral groups the allocated access was not attempted
P=077 Plt0001
TIMI lt3 andor final stenosis gt30
88
103
15 significant reduction at nominal 5 alpha
which is however NOT significant at the pre-specificed
alpha of 25
Primary EP MACE
Femoral
Radial
Rate Ratio 083 95 CI 073 to 096 p=00092
117
98
NNTB 53 Femoral
Radial
Primary EP NACE
Mortalidad Total
IAM
Fatal and ST EPs All-Cause Cardiac non-CV mortality type of stent thrombosis
RR072
(053-099)
P=0045
RR 075
(054-104)
P=008 1
13
06
1
0
02
04
06
08
1
12
14
Radial Femoral
P=069
P=066
Mortality Stent Thrombosis
NNTB 167
Bleeding endpoints BARC TIMI GUSTO access vs non-access related
14
25
P=0013
RR 067 049-092
P=00004
RR 037 021-066
BARC 3 or 5
P=00098
RR 064 045-090
P=008
RR 072 050-104 P=020
RR 078 053-114
Major
or minor
moderate
or severe
P=082
P=068
Rardial Better Femoral Better 1
HAZARD RATIO (95 CI)
P-VALUES
Superiority Interaction
089 Intermediate (548-991)
075 (060-094)
104 (082-132) 076 0011
Centrersquos annual
volume of PCI
Low (247-544)
Intermediate (654-790)
Centrersquos
Proportion of
radial PCI
Low (149-644)
NSTE-ACS (tpndash) ACS type
STEMI
lt75 Age
ge75 023 088 (070-109)
082 (068-097) 0023 062
NACE Subgroup Analysis
High (1000-1950)
High (800-980)
NSTE-ACS (tp+)
Men Sex
Women
lt25 BMI
ge25
No
Ticagrelor or
prasugrel Yes
No Diabetes
Yes
lt60 GFR
ge60
No
History of
PVD Yes
2 025 050
075 (058-097) 0025
00048
101 (079-129)
095 (075 -122) 071
095
064 (051-080) lt0001
044
086 (068-108)
058 (033-103) 0059
019
085 (071-102) 007
0012 072 (056-093)
089 (076-105) 016 018
009 086 (073-102)
079 (063-099) 0038 053
007 083 (068-102)
084 (070-101) 006 094
045 091 (071-117)
080 (068-094) 008 043
001 078 (065-094)
086 (070-107) 018 051
060 091 (064-130)
083 (071-096) 0012 064
Radial Better Femoral Better 1
HAZARD RATIO (95 CI)
P-VALUES
Superiority Interaction
Intermediate (654-790)
Centrersquos
Proportion
of radial PCI
Low (149-644)
NSTE-ACS (tpndash) ACS
type
STEMI
Subgroup Analysis
High (800-980)
NSTE-ACS (tp+)
2
00157
128 (071-232)
069 (040 -119) 018
041
048 (028-081) 0006
010
087 (059-129) 049
049 (028-087) 0012
Intermediate (654-790) Centrersquos
Proportion
of radial PCI
Low (149-644)
NSTE-ACS (tpndash) ACS
type
STEMI
High (800-980)
NSTE-ACS (tp+)
020
090 (054-150)
057 (031 -103) 006
068
056 (032-097) 0035
054
062 (041-094)
166 (028-100) 058
0022
070 (042-117) 017
Mortality
Bleeding
4 050 025
1 2 050 025
Updated Meta-analysis 19328 ACS patients being randomly allocated to radial or femoral access
Rardial Better Femoral Better 1 4 025 050 2
Pre-Rival RIVAL Post-RIVAL MATRI
X Combined
Non-CABG
major bleeds
Death
myocardial
infarction or
stroke
Death
Myocardial
Infarction
Stroke
Pre-Rival RIVAL Post-RIVAL MATRI
X Combined
Pre-Rival RIVAL Post-RIVAL MATRI
X Combined
Pre-Rival RIVAL Post-RIVAL MATRI
X Combined
Pre-Rival RIVAL Post-RIVAL MATRI
X Combined
SUBGROUP Risk Ratio (95CI) P Value
Heterogenity
P Value I2
073 (043-123) 039 (023-067)
058 (046-072)
041 (022-076)
lt00001 0 05
1
067 (048-093) 086 (076-098) 086 (077-095)
098 (076-127)
00051 0 09
7
058 (039-087) 073 (053-099) 072 (060-088) 00011 0 10
0
085 (039-190) 091 (078-106) 091 (079-104)
092 (065-131)
01
6 0 08
8
068 (049-092)
082 (052-129)
077 (046-128) 086 (058-129)
073 (012-447)
140 (045-440) 100 (050-200) 105 (069-160)
143 (072-283)
08
0 0 07
5
026 (006-123)
Summary bull Among patients with an ACS with or without ST-segment
elevation who underwent invasive management the use
of radial access for coronary angiography plusmn PCI reduced
the rate of net adverse clinical events with a number
needed to treat for benefit of 53
ndash Differences between groups were driven by reductions in BARC
major bleeding unrelated to CABG and all-cause mortality with
radial access
bull Our results in conjunction with the updated meta-
analysis suggest that radial approach should
become the default access for patients with
ACS undergoing invasive management
Radial Acces 61000 menos Muertes
LA VIA TRANSRADIAL DEBERIA SER EL ACCESO DE ELECCION o ldquo DEFAULTrdquo PARA LOS PACIENTES CON SCA TRATADOS CON INTERVENCIONISMO PERCUTANEO
LA VIA TRANSRADIAL DEBERIA SER EL ACCESO DE ELECCION PARA TODO PACIENTE CONSIN SCA TRATADOS CON INTERVENCIONISMO PERCUTANEO
GRACIAS POR SU ATENCION
MACE
Mortality
No interaction between access and anticoagulant use in a post- hoc analysis of the subgroup of 7213 patients randomized to bivalirudin or unfractionated heparin for the two co-primary outcomes all-cause mortality or BARC 3 or 5 bleeding
Relevance of bleeding as a clinical endpoint
bull Availability of potent antithrombotic therapy including ndash ASA ndash P2Y12 inhibitors (clopidogrel prasugrel ticagrelor) ndash heparin ndash GP IIbIIIa inhibitors ndash direct thrombin inhibitors
bull has led to a reduction in ischemic events bull but is associated with an increased risk of
bleeding bull the increase in bleeding is associated with worse
clinical outcome
Rationale for a new bleeding definition
bull Increased importance of bleeding as prognostic factor
bull Need for assessment of bleeding in RCTs and registries
bull Lack of comparability bull Need for standardized definitions to avoid
erroneous conclusions
ndash regarding safety of a given agent ndash regarding superiority of one agent over another
Open questions regarding BARC
bull Why 48-hour window for CABG-related bleeding
bull Why type 1 bdquonot actionableldquo when patient may bdquotake actionldquo such as discontinuing medication (with potentially serious consequences such as ST)
bull Why consider intraocular bleed equivalent to intracranial bleed for BARC 3c
bull Type 1 bleed subject to misinterpretation by the patient
Hicks et al (editorial) Circulation 20111232664
Conclusion
bull BARC is a new objective hierarchically graded classification of bleeding
(Mehran Circulation [June 14] 20111232736)
bull BARC is based on consensus rather than data-driven
bull Prospective validation is warranted ndash across the spectrum of IHD
ndash across management strategies (conservative invasive)
ndash in the context of all invasive procedures (PCI CABG endovascular TAVI)
Conclusion (2)
bull Final validation of BARC and proof of its utility depend on
ndash its use by all future RCTs as common safety endpoint
ndash unanimous assessment procedure (questionnaires)
bull More important than using one or the other bleeding risk score is the agreement and commitment among clinical trialists to use the same score for comparability of data
SUPERVIVENCIA SEGUacuteN ACCESO VASCULAR
p lt 001
diacuteas
AF 057
AR 068
CONCLUSIONES
El ACCESO RADIAL se asocioacute a disminucioacuten del riesgo de
MUERTE a corto y largo plazo en el tratamiento intervencionista
del IAMcST y por tanto PODRIA SER LA VIA DE ABORDAJE DE
ELECCION EN ESTOS PACIENTES
Adoption of Radial Access in PCI in US Trend in the Use of r-PCI Over Time in the Overall amp Key Subgroups
Feldman et al Circulation 20131272295
All Patients
Pts with Stable angina NSTE ACS STEMI
Overall Radial PCI
R
ad
ial
20
07
- Q
tr
20
07
- Q
tr
20
08
- Q
tr
20
08
- Q
tr
20
09
- Q
tr
20
09
- Q
tr
20
10
- Q
tr
20
10
- Q
tr
20
11
- Q
tr
20
11
- Q
tr
20
12
- Q
tr
20
12
- Q
tr
20
18
16
14
12
10
8
6
4
2
161
R
ad
ial
20
07
- Q
tr
20
07
- Q
tr
20
08
- Q
tr
20
08
- Q
tr
20
09
- Q
tr
20
09
- Q
tr
20
10
- Q
tr
20
10
- Q
tr
20
11
- Q
tr
20
11
- Q
tr
20
12
- Q
tr
20
12
- Q
tr
Male Female 20
18
16
14
12
10
8
6
4
2
R
ad
ial
20
07
- Q
tr
20
07
- Q
tr
20
08
- Q
tr
20
08
- Q
tr
20
09
- Q
tr
20
09
- Q
tr
20
10
- Q
tr
20
10
- Q
tr
20
11
- Q
tr
20
11
- Q
tr
20
12
- Q
tr
20
12
- Q
tr
UANSTEMI STEMI Stable Angina 2
0
1
8
1
6
1
4
1
2
1
0
8
6
4
2
IAM
bull All antithrombotic agents (except fondaparinux bivalirudin) are associated with increased bleeding risk
bull Aspirin and heparin reduce death MI at 30 days in NSTE-ACS
Choice of arterial access site and outcomes in patients with acute coronary
siacutendromes managed with an early invasive strategy the ACUITY trial Hamon M Rasmussen LH Manoukian SV Cequier A Lincoff MA Rupprecht HJ Gersh BJ Mann T Bertrand ME Mehran R Stone GW
AIMS The purpose of this study was to evaluate the impact of arterial access site on bleeding and ischaemic outcomes overall and by
treatment strategy in patients with acute coronary syndromes (ACS)
METHODS AND RESULTS In the ACUITY trial 13819 patients with moderate and high-risk ACS were randomised to either heparin
(unfractionated or enoxaparin) plus a glycoprotein IIbIIIa inhibitor (GPI) bivalirudin plus a GPI or bivalirudin alone
Per operator choice femoral access was utilised in 11989 patients (938) and radial Access in 798 patients (62) There was no significant
difference in composite ischaemia between the radial and femoral approaches at 30 days (81 vs 75 p=018) or 1 year (147 vs
155 p=077)although fewer major bleeding complications occurred with the use of radial access (30vs48 p=003) Use of
bivalirudin monotherapy was associated with significantly less 30-day major bleeding than heparin plus GPI after femoral access
(30 vs 58 plt00001) but not with radial access (42 vs 22 P=019)
Major or minor organ bleeding was reduced with bivalirudin monotherapy compared to heparin plus GPI to a similar extent with both
femoral (41 vs 74 Plt00001) and radial (49 vs 72 P=026) access
EuroIntervention 2009 May5(1)115-20
CONCLUSIONS
Transradial compared to femoral arterial access is associated with similar rates of composite ischaemia
anwith fewer major bleeding complications in patients with ACS managed invasively
Bivalirudin monotherapy compared to heparin plus GPIs significantly reduces
access site related major bleeding complications with femoral
but not radial artery access though non-access site related bleeding is reduced by
bivalirudin monotherapy in all patients
0 5 10 15 20 25 30
0
20
40
60
80
100
120
140
Mo
rta
lity
(
)
CURE=Clopidogrel in Unstable angina to prevent Recurrent ischemic Events (study) OASIS=Organization to Assess
Strategies for Ischemic Syndromes (study)
Reproduced with permission from Eikelboom JW et al Circulation 2006114774-782
Major Bleeding During First 30 Days Is Associated With Mortality Meta-analysis of 34146
ACS patients from the randomized OASIS OASIS-2 and CURE trials assessed the
association between bleeding within the first 30 days and death
Without major bleeding
With major bleeding
Days
Mo
rtality
(
)
Days from randomization
0 30 60 90 120 150 180 210 240 270 300 330 360 390
0
5
15
30
10
25
20
Major bleed only (without MI) (n=551)
Both MI and major bleed (n=94)
No MI or major bleed (n=12557)
MI only (without major bleed) (n=611)
Data on file The Medicines Company Parsippany NJ
289
125
86
34
Univariate analysis of 13819 patients from ACUITY
Impact of Non-CABG Major Bleeding and
MI at 30 Days on 1-Year Mortality
Radial Access 798 pts 62
Am Heart J 2009 Jan157(1)164-9 Epub 2008 Nov 6
Am Heart J 2009 Jan157(1)164-9 Epub 2008 Nov 6
Hypothetical mechanisms linking bleeding and mortality
Steg P G et al Eur Heart J 2011321854-
1864
Existing bleeding scores
bull TIMI Laboratory-based (hemoglobin hematocrit decrease)
bull GUSTO Clinical (severity)-based
bull GRACE Simplified laboratory and clinical
bull CURE Major minor (combined clin + lab)
bull ACUITY Major (intracranial-ocular access-site retroperit) lab
bull REPLACE-2 bull ISAR-REACT 3 bull PLATO bull STEEPLE bull CURRENT-OASIS
Thrombolysis conservative
PCI-based
BARC (Bleeding Academic Research Consortium) definitions
Mehran et al Circulation 20111232736-2747
bull Type 0 no evidence of bleeding bull Type 1 bleeding that is not actionable without
need for hospitalization or treatment (eg bruising hematoma nosebleeds etc)
bull Type 2 any clinically overt sign of hemorrhage that is actionable but does not meet criteria for type 3 4 or 5 Must meet at least 1 of following criteria ndash Requires intervention ndash Leads to hospitalization MANEJO MEDICO ndash Prompts evaluation
BARC (Bleeding Academic Research Consortium) definitions
Mehran et al Circulation 20111232736-2747
bull Type 3 clinical laboratory andor imaging evidence of bleeding with healthcare provider responses ndash BARC type 3a
bull any transfusion with overt bleeding bull overt bleeding plus hemoglobin drop ge3 to lt5 gdL
ndash BARC type 3b bull overt bleeding plus hemoglobin drop gt5 gdL bull Cardiac tamponade bull Bleeding requiring surgical intervention for control (excluding dentalnasalskinhemorrhoid) bull Bleeding requiring intravenous vasoactive drugs
ndash BARC type 3c bull Intracranial hemorrhage subcategories confirmed by autopsy
imaging or lumbar puncture bull Intraocular bleed compromising vision
BARC Bleeding Academic Research Consortium) definitions
Mehran et al Circulation 20111232736-2747
bull Type 4 Coronary Artery Bypass Graftndashrelated bleeding ndash Perioperative intracranial bleeding within 48 hours ndash Reoperation after closure of sternotomy for the purpose of controlling bleeding ndash Transfusion of ge5 U whole blood or packed red blood cells within a 48-hour period ndash Chest tube output 2 L within a 24-hour period
bull Type 5 ndash fatal bleeding bull Probable fatal bleeding (type 5a)
ndash bleeding that is clinically suspicious as the cause of death but the bleeding is not directly observed and there is no autopsy or confirmatory imaging
bull Definite fatal bleeding (type 5b) ndash bleeding that is directly observed (by either clinical specimen [blood
emesis stool etc] or imaging) or confirmed on autopsy
26 VCD
11
NSTEACS or STEMI with invasive management Aspirin+P2Y12 blocker
Trans-Femoral Access
Trans-Radial Access
To demonstrate that trans-radial intervention as
compared to femoral access site is associated to lower
rate of the composite endpoint of Death MI or Stroke
within the first 30 days
1deg co-Primary Objective
6 vs 42 βlt10 α 25 8200 patients
Adaptive study Design sample size (SS) will be increased
by the cross-over rate at 70 of planned SS
MATRIX Access site NCT01433627
MATRIX Access
39 93 132 200 276 380 490 685 857 1002 1190
1400 1684 1972 2248
2584 2926
3256 3560
3875 4144
4452 4726
5000 5322
5655 5896 6184
6458 6742 6982 7235 7444 7638 7844 8073
8404
Cumulative enrollment by month
8404
8404
8404 patients with ACS undergoing coronary angiography plusmn PCI from 11th Oct 2011 to 7th Nov 2014
Operator Eligibility Criteria Interventional cardiologist expertise in TRI and TFI including at least 75 transradial coronary interventions and at least 50 of interventions performed via radial route in the year preceding site initiation
Complete follow-up to 30 days available in 4183 (997) of radial and 4191 (99middot6) of femoral cohorts
Am Heart J 2014 Dec168(6)838-45e6
Cross Over and Procedural Success Rates
941 of radial and 974 of femoral cohorts received respective treatment as allocated
In 58 of radial and 23 of TF cohort the allocated access was attempted but failed
In 3 (01) in the radial and 13 (03) patients in the femoral groups the allocated access was not attempted
P=077 Plt0001
TIMI lt3 andor final stenosis gt30
88
103
15 significant reduction at nominal 5 alpha
which is however NOT significant at the pre-specificed
alpha of 25
Primary EP MACE
Femoral
Radial
Rate Ratio 083 95 CI 073 to 096 p=00092
117
98
NNTB 53 Femoral
Radial
Primary EP NACE
Mortalidad Total
IAM
Fatal and ST EPs All-Cause Cardiac non-CV mortality type of stent thrombosis
RR072
(053-099)
P=0045
RR 075
(054-104)
P=008 1
13
06
1
0
02
04
06
08
1
12
14
Radial Femoral
P=069
P=066
Mortality Stent Thrombosis
NNTB 167
Bleeding endpoints BARC TIMI GUSTO access vs non-access related
14
25
P=0013
RR 067 049-092
P=00004
RR 037 021-066
BARC 3 or 5
P=00098
RR 064 045-090
P=008
RR 072 050-104 P=020
RR 078 053-114
Major
or minor
moderate
or severe
P=082
P=068
Rardial Better Femoral Better 1
HAZARD RATIO (95 CI)
P-VALUES
Superiority Interaction
089 Intermediate (548-991)
075 (060-094)
104 (082-132) 076 0011
Centrersquos annual
volume of PCI
Low (247-544)
Intermediate (654-790)
Centrersquos
Proportion of
radial PCI
Low (149-644)
NSTE-ACS (tpndash) ACS type
STEMI
lt75 Age
ge75 023 088 (070-109)
082 (068-097) 0023 062
NACE Subgroup Analysis
High (1000-1950)
High (800-980)
NSTE-ACS (tp+)
Men Sex
Women
lt25 BMI
ge25
No
Ticagrelor or
prasugrel Yes
No Diabetes
Yes
lt60 GFR
ge60
No
History of
PVD Yes
2 025 050
075 (058-097) 0025
00048
101 (079-129)
095 (075 -122) 071
095
064 (051-080) lt0001
044
086 (068-108)
058 (033-103) 0059
019
085 (071-102) 007
0012 072 (056-093)
089 (076-105) 016 018
009 086 (073-102)
079 (063-099) 0038 053
007 083 (068-102)
084 (070-101) 006 094
045 091 (071-117)
080 (068-094) 008 043
001 078 (065-094)
086 (070-107) 018 051
060 091 (064-130)
083 (071-096) 0012 064
Radial Better Femoral Better 1
HAZARD RATIO (95 CI)
P-VALUES
Superiority Interaction
Intermediate (654-790)
Centrersquos
Proportion
of radial PCI
Low (149-644)
NSTE-ACS (tpndash) ACS
type
STEMI
Subgroup Analysis
High (800-980)
NSTE-ACS (tp+)
2
00157
128 (071-232)
069 (040 -119) 018
041
048 (028-081) 0006
010
087 (059-129) 049
049 (028-087) 0012
Intermediate (654-790) Centrersquos
Proportion
of radial PCI
Low (149-644)
NSTE-ACS (tpndash) ACS
type
STEMI
High (800-980)
NSTE-ACS (tp+)
020
090 (054-150)
057 (031 -103) 006
068
056 (032-097) 0035
054
062 (041-094)
166 (028-100) 058
0022
070 (042-117) 017
Mortality
Bleeding
4 050 025
1 2 050 025
Updated Meta-analysis 19328 ACS patients being randomly allocated to radial or femoral access
Rardial Better Femoral Better 1 4 025 050 2
Pre-Rival RIVAL Post-RIVAL MATRI
X Combined
Non-CABG
major bleeds
Death
myocardial
infarction or
stroke
Death
Myocardial
Infarction
Stroke
Pre-Rival RIVAL Post-RIVAL MATRI
X Combined
Pre-Rival RIVAL Post-RIVAL MATRI
X Combined
Pre-Rival RIVAL Post-RIVAL MATRI
X Combined
Pre-Rival RIVAL Post-RIVAL MATRI
X Combined
SUBGROUP Risk Ratio (95CI) P Value
Heterogenity
P Value I2
073 (043-123) 039 (023-067)
058 (046-072)
041 (022-076)
lt00001 0 05
1
067 (048-093) 086 (076-098) 086 (077-095)
098 (076-127)
00051 0 09
7
058 (039-087) 073 (053-099) 072 (060-088) 00011 0 10
0
085 (039-190) 091 (078-106) 091 (079-104)
092 (065-131)
01
6 0 08
8
068 (049-092)
082 (052-129)
077 (046-128) 086 (058-129)
073 (012-447)
140 (045-440) 100 (050-200) 105 (069-160)
143 (072-283)
08
0 0 07
5
026 (006-123)
Summary bull Among patients with an ACS with or without ST-segment
elevation who underwent invasive management the use
of radial access for coronary angiography plusmn PCI reduced
the rate of net adverse clinical events with a number
needed to treat for benefit of 53
ndash Differences between groups were driven by reductions in BARC
major bleeding unrelated to CABG and all-cause mortality with
radial access
bull Our results in conjunction with the updated meta-
analysis suggest that radial approach should
become the default access for patients with
ACS undergoing invasive management
Radial Acces 61000 menos Muertes
LA VIA TRANSRADIAL DEBERIA SER EL ACCESO DE ELECCION o ldquo DEFAULTrdquo PARA LOS PACIENTES CON SCA TRATADOS CON INTERVENCIONISMO PERCUTANEO
LA VIA TRANSRADIAL DEBERIA SER EL ACCESO DE ELECCION PARA TODO PACIENTE CONSIN SCA TRATADOS CON INTERVENCIONISMO PERCUTANEO
GRACIAS POR SU ATENCION
MACE
Mortality
No interaction between access and anticoagulant use in a post- hoc analysis of the subgroup of 7213 patients randomized to bivalirudin or unfractionated heparin for the two co-primary outcomes all-cause mortality or BARC 3 or 5 bleeding
Relevance of bleeding as a clinical endpoint
bull Availability of potent antithrombotic therapy including ndash ASA ndash P2Y12 inhibitors (clopidogrel prasugrel ticagrelor) ndash heparin ndash GP IIbIIIa inhibitors ndash direct thrombin inhibitors
bull has led to a reduction in ischemic events bull but is associated with an increased risk of
bleeding bull the increase in bleeding is associated with worse
clinical outcome
Rationale for a new bleeding definition
bull Increased importance of bleeding as prognostic factor
bull Need for assessment of bleeding in RCTs and registries
bull Lack of comparability bull Need for standardized definitions to avoid
erroneous conclusions
ndash regarding safety of a given agent ndash regarding superiority of one agent over another
Open questions regarding BARC
bull Why 48-hour window for CABG-related bleeding
bull Why type 1 bdquonot actionableldquo when patient may bdquotake actionldquo such as discontinuing medication (with potentially serious consequences such as ST)
bull Why consider intraocular bleed equivalent to intracranial bleed for BARC 3c
bull Type 1 bleed subject to misinterpretation by the patient
Hicks et al (editorial) Circulation 20111232664
Conclusion
bull BARC is a new objective hierarchically graded classification of bleeding
(Mehran Circulation [June 14] 20111232736)
bull BARC is based on consensus rather than data-driven
bull Prospective validation is warranted ndash across the spectrum of IHD
ndash across management strategies (conservative invasive)
ndash in the context of all invasive procedures (PCI CABG endovascular TAVI)
Conclusion (2)
bull Final validation of BARC and proof of its utility depend on
ndash its use by all future RCTs as common safety endpoint
ndash unanimous assessment procedure (questionnaires)
bull More important than using one or the other bleeding risk score is the agreement and commitment among clinical trialists to use the same score for comparability of data
CONCLUSIONES
El ACCESO RADIAL se asocioacute a disminucioacuten del riesgo de
MUERTE a corto y largo plazo en el tratamiento intervencionista
del IAMcST y por tanto PODRIA SER LA VIA DE ABORDAJE DE
ELECCION EN ESTOS PACIENTES
Adoption of Radial Access in PCI in US Trend in the Use of r-PCI Over Time in the Overall amp Key Subgroups
Feldman et al Circulation 20131272295
All Patients
Pts with Stable angina NSTE ACS STEMI
Overall Radial PCI
R
ad
ial
20
07
- Q
tr
20
07
- Q
tr
20
08
- Q
tr
20
08
- Q
tr
20
09
- Q
tr
20
09
- Q
tr
20
10
- Q
tr
20
10
- Q
tr
20
11
- Q
tr
20
11
- Q
tr
20
12
- Q
tr
20
12
- Q
tr
20
18
16
14
12
10
8
6
4
2
161
R
ad
ial
20
07
- Q
tr
20
07
- Q
tr
20
08
- Q
tr
20
08
- Q
tr
20
09
- Q
tr
20
09
- Q
tr
20
10
- Q
tr
20
10
- Q
tr
20
11
- Q
tr
20
11
- Q
tr
20
12
- Q
tr
20
12
- Q
tr
Male Female 20
18
16
14
12
10
8
6
4
2
R
ad
ial
20
07
- Q
tr
20
07
- Q
tr
20
08
- Q
tr
20
08
- Q
tr
20
09
- Q
tr
20
09
- Q
tr
20
10
- Q
tr
20
10
- Q
tr
20
11
- Q
tr
20
11
- Q
tr
20
12
- Q
tr
20
12
- Q
tr
UANSTEMI STEMI Stable Angina 2
0
1
8
1
6
1
4
1
2
1
0
8
6
4
2
IAM
bull All antithrombotic agents (except fondaparinux bivalirudin) are associated with increased bleeding risk
bull Aspirin and heparin reduce death MI at 30 days in NSTE-ACS
Choice of arterial access site and outcomes in patients with acute coronary
siacutendromes managed with an early invasive strategy the ACUITY trial Hamon M Rasmussen LH Manoukian SV Cequier A Lincoff MA Rupprecht HJ Gersh BJ Mann T Bertrand ME Mehran R Stone GW
AIMS The purpose of this study was to evaluate the impact of arterial access site on bleeding and ischaemic outcomes overall and by
treatment strategy in patients with acute coronary syndromes (ACS)
METHODS AND RESULTS In the ACUITY trial 13819 patients with moderate and high-risk ACS were randomised to either heparin
(unfractionated or enoxaparin) plus a glycoprotein IIbIIIa inhibitor (GPI) bivalirudin plus a GPI or bivalirudin alone
Per operator choice femoral access was utilised in 11989 patients (938) and radial Access in 798 patients (62) There was no significant
difference in composite ischaemia between the radial and femoral approaches at 30 days (81 vs 75 p=018) or 1 year (147 vs
155 p=077)although fewer major bleeding complications occurred with the use of radial access (30vs48 p=003) Use of
bivalirudin monotherapy was associated with significantly less 30-day major bleeding than heparin plus GPI after femoral access
(30 vs 58 plt00001) but not with radial access (42 vs 22 P=019)
Major or minor organ bleeding was reduced with bivalirudin monotherapy compared to heparin plus GPI to a similar extent with both
femoral (41 vs 74 Plt00001) and radial (49 vs 72 P=026) access
EuroIntervention 2009 May5(1)115-20
CONCLUSIONS
Transradial compared to femoral arterial access is associated with similar rates of composite ischaemia
anwith fewer major bleeding complications in patients with ACS managed invasively
Bivalirudin monotherapy compared to heparin plus GPIs significantly reduces
access site related major bleeding complications with femoral
but not radial artery access though non-access site related bleeding is reduced by
bivalirudin monotherapy in all patients
0 5 10 15 20 25 30
0
20
40
60
80
100
120
140
Mo
rta
lity
(
)
CURE=Clopidogrel in Unstable angina to prevent Recurrent ischemic Events (study) OASIS=Organization to Assess
Strategies for Ischemic Syndromes (study)
Reproduced with permission from Eikelboom JW et al Circulation 2006114774-782
Major Bleeding During First 30 Days Is Associated With Mortality Meta-analysis of 34146
ACS patients from the randomized OASIS OASIS-2 and CURE trials assessed the
association between bleeding within the first 30 days and death
Without major bleeding
With major bleeding
Days
Mo
rtality
(
)
Days from randomization
0 30 60 90 120 150 180 210 240 270 300 330 360 390
0
5
15
30
10
25
20
Major bleed only (without MI) (n=551)
Both MI and major bleed (n=94)
No MI or major bleed (n=12557)
MI only (without major bleed) (n=611)
Data on file The Medicines Company Parsippany NJ
289
125
86
34
Univariate analysis of 13819 patients from ACUITY
Impact of Non-CABG Major Bleeding and
MI at 30 Days on 1-Year Mortality
Radial Access 798 pts 62
Am Heart J 2009 Jan157(1)164-9 Epub 2008 Nov 6
Am Heart J 2009 Jan157(1)164-9 Epub 2008 Nov 6
Hypothetical mechanisms linking bleeding and mortality
Steg P G et al Eur Heart J 2011321854-
1864
Existing bleeding scores
bull TIMI Laboratory-based (hemoglobin hematocrit decrease)
bull GUSTO Clinical (severity)-based
bull GRACE Simplified laboratory and clinical
bull CURE Major minor (combined clin + lab)
bull ACUITY Major (intracranial-ocular access-site retroperit) lab
bull REPLACE-2 bull ISAR-REACT 3 bull PLATO bull STEEPLE bull CURRENT-OASIS
Thrombolysis conservative
PCI-based
BARC (Bleeding Academic Research Consortium) definitions
Mehran et al Circulation 20111232736-2747
bull Type 0 no evidence of bleeding bull Type 1 bleeding that is not actionable without
need for hospitalization or treatment (eg bruising hematoma nosebleeds etc)
bull Type 2 any clinically overt sign of hemorrhage that is actionable but does not meet criteria for type 3 4 or 5 Must meet at least 1 of following criteria ndash Requires intervention ndash Leads to hospitalization MANEJO MEDICO ndash Prompts evaluation
BARC (Bleeding Academic Research Consortium) definitions
Mehran et al Circulation 20111232736-2747
bull Type 3 clinical laboratory andor imaging evidence of bleeding with healthcare provider responses ndash BARC type 3a
bull any transfusion with overt bleeding bull overt bleeding plus hemoglobin drop ge3 to lt5 gdL
ndash BARC type 3b bull overt bleeding plus hemoglobin drop gt5 gdL bull Cardiac tamponade bull Bleeding requiring surgical intervention for control (excluding dentalnasalskinhemorrhoid) bull Bleeding requiring intravenous vasoactive drugs
ndash BARC type 3c bull Intracranial hemorrhage subcategories confirmed by autopsy
imaging or lumbar puncture bull Intraocular bleed compromising vision
BARC Bleeding Academic Research Consortium) definitions
Mehran et al Circulation 20111232736-2747
bull Type 4 Coronary Artery Bypass Graftndashrelated bleeding ndash Perioperative intracranial bleeding within 48 hours ndash Reoperation after closure of sternotomy for the purpose of controlling bleeding ndash Transfusion of ge5 U whole blood or packed red blood cells within a 48-hour period ndash Chest tube output 2 L within a 24-hour period
bull Type 5 ndash fatal bleeding bull Probable fatal bleeding (type 5a)
ndash bleeding that is clinically suspicious as the cause of death but the bleeding is not directly observed and there is no autopsy or confirmatory imaging
bull Definite fatal bleeding (type 5b) ndash bleeding that is directly observed (by either clinical specimen [blood
emesis stool etc] or imaging) or confirmed on autopsy
26 VCD
11
NSTEACS or STEMI with invasive management Aspirin+P2Y12 blocker
Trans-Femoral Access
Trans-Radial Access
To demonstrate that trans-radial intervention as
compared to femoral access site is associated to lower
rate of the composite endpoint of Death MI or Stroke
within the first 30 days
1deg co-Primary Objective
6 vs 42 βlt10 α 25 8200 patients
Adaptive study Design sample size (SS) will be increased
by the cross-over rate at 70 of planned SS
MATRIX Access site NCT01433627
MATRIX Access
39 93 132 200 276 380 490 685 857 1002 1190
1400 1684 1972 2248
2584 2926
3256 3560
3875 4144
4452 4726
5000 5322
5655 5896 6184
6458 6742 6982 7235 7444 7638 7844 8073
8404
Cumulative enrollment by month
8404
8404
8404 patients with ACS undergoing coronary angiography plusmn PCI from 11th Oct 2011 to 7th Nov 2014
Operator Eligibility Criteria Interventional cardiologist expertise in TRI and TFI including at least 75 transradial coronary interventions and at least 50 of interventions performed via radial route in the year preceding site initiation
Complete follow-up to 30 days available in 4183 (997) of radial and 4191 (99middot6) of femoral cohorts
Am Heart J 2014 Dec168(6)838-45e6
Cross Over and Procedural Success Rates
941 of radial and 974 of femoral cohorts received respective treatment as allocated
In 58 of radial and 23 of TF cohort the allocated access was attempted but failed
In 3 (01) in the radial and 13 (03) patients in the femoral groups the allocated access was not attempted
P=077 Plt0001
TIMI lt3 andor final stenosis gt30
88
103
15 significant reduction at nominal 5 alpha
which is however NOT significant at the pre-specificed
alpha of 25
Primary EP MACE
Femoral
Radial
Rate Ratio 083 95 CI 073 to 096 p=00092
117
98
NNTB 53 Femoral
Radial
Primary EP NACE
Mortalidad Total
IAM
Fatal and ST EPs All-Cause Cardiac non-CV mortality type of stent thrombosis
RR072
(053-099)
P=0045
RR 075
(054-104)
P=008 1
13
06
1
0
02
04
06
08
1
12
14
Radial Femoral
P=069
P=066
Mortality Stent Thrombosis
NNTB 167
Bleeding endpoints BARC TIMI GUSTO access vs non-access related
14
25
P=0013
RR 067 049-092
P=00004
RR 037 021-066
BARC 3 or 5
P=00098
RR 064 045-090
P=008
RR 072 050-104 P=020
RR 078 053-114
Major
or minor
moderate
or severe
P=082
P=068
Rardial Better Femoral Better 1
HAZARD RATIO (95 CI)
P-VALUES
Superiority Interaction
089 Intermediate (548-991)
075 (060-094)
104 (082-132) 076 0011
Centrersquos annual
volume of PCI
Low (247-544)
Intermediate (654-790)
Centrersquos
Proportion of
radial PCI
Low (149-644)
NSTE-ACS (tpndash) ACS type
STEMI
lt75 Age
ge75 023 088 (070-109)
082 (068-097) 0023 062
NACE Subgroup Analysis
High (1000-1950)
High (800-980)
NSTE-ACS (tp+)
Men Sex
Women
lt25 BMI
ge25
No
Ticagrelor or
prasugrel Yes
No Diabetes
Yes
lt60 GFR
ge60
No
History of
PVD Yes
2 025 050
075 (058-097) 0025
00048
101 (079-129)
095 (075 -122) 071
095
064 (051-080) lt0001
044
086 (068-108)
058 (033-103) 0059
019
085 (071-102) 007
0012 072 (056-093)
089 (076-105) 016 018
009 086 (073-102)
079 (063-099) 0038 053
007 083 (068-102)
084 (070-101) 006 094
045 091 (071-117)
080 (068-094) 008 043
001 078 (065-094)
086 (070-107) 018 051
060 091 (064-130)
083 (071-096) 0012 064
Radial Better Femoral Better 1
HAZARD RATIO (95 CI)
P-VALUES
Superiority Interaction
Intermediate (654-790)
Centrersquos
Proportion
of radial PCI
Low (149-644)
NSTE-ACS (tpndash) ACS
type
STEMI
Subgroup Analysis
High (800-980)
NSTE-ACS (tp+)
2
00157
128 (071-232)
069 (040 -119) 018
041
048 (028-081) 0006
010
087 (059-129) 049
049 (028-087) 0012
Intermediate (654-790) Centrersquos
Proportion
of radial PCI
Low (149-644)
NSTE-ACS (tpndash) ACS
type
STEMI
High (800-980)
NSTE-ACS (tp+)
020
090 (054-150)
057 (031 -103) 006
068
056 (032-097) 0035
054
062 (041-094)
166 (028-100) 058
0022
070 (042-117) 017
Mortality
Bleeding
4 050 025
1 2 050 025
Updated Meta-analysis 19328 ACS patients being randomly allocated to radial or femoral access
Rardial Better Femoral Better 1 4 025 050 2
Pre-Rival RIVAL Post-RIVAL MATRI
X Combined
Non-CABG
major bleeds
Death
myocardial
infarction or
stroke
Death
Myocardial
Infarction
Stroke
Pre-Rival RIVAL Post-RIVAL MATRI
X Combined
Pre-Rival RIVAL Post-RIVAL MATRI
X Combined
Pre-Rival RIVAL Post-RIVAL MATRI
X Combined
Pre-Rival RIVAL Post-RIVAL MATRI
X Combined
SUBGROUP Risk Ratio (95CI) P Value
Heterogenity
P Value I2
073 (043-123) 039 (023-067)
058 (046-072)
041 (022-076)
lt00001 0 05
1
067 (048-093) 086 (076-098) 086 (077-095)
098 (076-127)
00051 0 09
7
058 (039-087) 073 (053-099) 072 (060-088) 00011 0 10
0
085 (039-190) 091 (078-106) 091 (079-104)
092 (065-131)
01
6 0 08
8
068 (049-092)
082 (052-129)
077 (046-128) 086 (058-129)
073 (012-447)
140 (045-440) 100 (050-200) 105 (069-160)
143 (072-283)
08
0 0 07
5
026 (006-123)
Summary bull Among patients with an ACS with or without ST-segment
elevation who underwent invasive management the use
of radial access for coronary angiography plusmn PCI reduced
the rate of net adverse clinical events with a number
needed to treat for benefit of 53
ndash Differences between groups were driven by reductions in BARC
major bleeding unrelated to CABG and all-cause mortality with
radial access
bull Our results in conjunction with the updated meta-
analysis suggest that radial approach should
become the default access for patients with
ACS undergoing invasive management
Radial Acces 61000 menos Muertes
LA VIA TRANSRADIAL DEBERIA SER EL ACCESO DE ELECCION o ldquo DEFAULTrdquo PARA LOS PACIENTES CON SCA TRATADOS CON INTERVENCIONISMO PERCUTANEO
LA VIA TRANSRADIAL DEBERIA SER EL ACCESO DE ELECCION PARA TODO PACIENTE CONSIN SCA TRATADOS CON INTERVENCIONISMO PERCUTANEO
GRACIAS POR SU ATENCION
MACE
Mortality
No interaction between access and anticoagulant use in a post- hoc analysis of the subgroup of 7213 patients randomized to bivalirudin or unfractionated heparin for the two co-primary outcomes all-cause mortality or BARC 3 or 5 bleeding
Relevance of bleeding as a clinical endpoint
bull Availability of potent antithrombotic therapy including ndash ASA ndash P2Y12 inhibitors (clopidogrel prasugrel ticagrelor) ndash heparin ndash GP IIbIIIa inhibitors ndash direct thrombin inhibitors
bull has led to a reduction in ischemic events bull but is associated with an increased risk of
bleeding bull the increase in bleeding is associated with worse
clinical outcome
Rationale for a new bleeding definition
bull Increased importance of bleeding as prognostic factor
bull Need for assessment of bleeding in RCTs and registries
bull Lack of comparability bull Need for standardized definitions to avoid
erroneous conclusions
ndash regarding safety of a given agent ndash regarding superiority of one agent over another
Open questions regarding BARC
bull Why 48-hour window for CABG-related bleeding
bull Why type 1 bdquonot actionableldquo when patient may bdquotake actionldquo such as discontinuing medication (with potentially serious consequences such as ST)
bull Why consider intraocular bleed equivalent to intracranial bleed for BARC 3c
bull Type 1 bleed subject to misinterpretation by the patient
Hicks et al (editorial) Circulation 20111232664
Conclusion
bull BARC is a new objective hierarchically graded classification of bleeding
(Mehran Circulation [June 14] 20111232736)
bull BARC is based on consensus rather than data-driven
bull Prospective validation is warranted ndash across the spectrum of IHD
ndash across management strategies (conservative invasive)
ndash in the context of all invasive procedures (PCI CABG endovascular TAVI)
Conclusion (2)
bull Final validation of BARC and proof of its utility depend on
ndash its use by all future RCTs as common safety endpoint
ndash unanimous assessment procedure (questionnaires)
bull More important than using one or the other bleeding risk score is the agreement and commitment among clinical trialists to use the same score for comparability of data
Adoption of Radial Access in PCI in US Trend in the Use of r-PCI Over Time in the Overall amp Key Subgroups
Feldman et al Circulation 20131272295
All Patients
Pts with Stable angina NSTE ACS STEMI
Overall Radial PCI
R
ad
ial
20
07
- Q
tr
20
07
- Q
tr
20
08
- Q
tr
20
08
- Q
tr
20
09
- Q
tr
20
09
- Q
tr
20
10
- Q
tr
20
10
- Q
tr
20
11
- Q
tr
20
11
- Q
tr
20
12
- Q
tr
20
12
- Q
tr
20
18
16
14
12
10
8
6
4
2
161
R
ad
ial
20
07
- Q
tr
20
07
- Q
tr
20
08
- Q
tr
20
08
- Q
tr
20
09
- Q
tr
20
09
- Q
tr
20
10
- Q
tr
20
10
- Q
tr
20
11
- Q
tr
20
11
- Q
tr
20
12
- Q
tr
20
12
- Q
tr
Male Female 20
18
16
14
12
10
8
6
4
2
R
ad
ial
20
07
- Q
tr
20
07
- Q
tr
20
08
- Q
tr
20
08
- Q
tr
20
09
- Q
tr
20
09
- Q
tr
20
10
- Q
tr
20
10
- Q
tr
20
11
- Q
tr
20
11
- Q
tr
20
12
- Q
tr
20
12
- Q
tr
UANSTEMI STEMI Stable Angina 2
0
1
8
1
6
1
4
1
2
1
0
8
6
4
2
IAM
bull All antithrombotic agents (except fondaparinux bivalirudin) are associated with increased bleeding risk
bull Aspirin and heparin reduce death MI at 30 days in NSTE-ACS
Choice of arterial access site and outcomes in patients with acute coronary
siacutendromes managed with an early invasive strategy the ACUITY trial Hamon M Rasmussen LH Manoukian SV Cequier A Lincoff MA Rupprecht HJ Gersh BJ Mann T Bertrand ME Mehran R Stone GW
AIMS The purpose of this study was to evaluate the impact of arterial access site on bleeding and ischaemic outcomes overall and by
treatment strategy in patients with acute coronary syndromes (ACS)
METHODS AND RESULTS In the ACUITY trial 13819 patients with moderate and high-risk ACS were randomised to either heparin
(unfractionated or enoxaparin) plus a glycoprotein IIbIIIa inhibitor (GPI) bivalirudin plus a GPI or bivalirudin alone
Per operator choice femoral access was utilised in 11989 patients (938) and radial Access in 798 patients (62) There was no significant
difference in composite ischaemia between the radial and femoral approaches at 30 days (81 vs 75 p=018) or 1 year (147 vs
155 p=077)although fewer major bleeding complications occurred with the use of radial access (30vs48 p=003) Use of
bivalirudin monotherapy was associated with significantly less 30-day major bleeding than heparin plus GPI after femoral access
(30 vs 58 plt00001) but not with radial access (42 vs 22 P=019)
Major or minor organ bleeding was reduced with bivalirudin monotherapy compared to heparin plus GPI to a similar extent with both
femoral (41 vs 74 Plt00001) and radial (49 vs 72 P=026) access
EuroIntervention 2009 May5(1)115-20
CONCLUSIONS
Transradial compared to femoral arterial access is associated with similar rates of composite ischaemia
anwith fewer major bleeding complications in patients with ACS managed invasively
Bivalirudin monotherapy compared to heparin plus GPIs significantly reduces
access site related major bleeding complications with femoral
but not radial artery access though non-access site related bleeding is reduced by
bivalirudin monotherapy in all patients
0 5 10 15 20 25 30
0
20
40
60
80
100
120
140
Mo
rta
lity
(
)
CURE=Clopidogrel in Unstable angina to prevent Recurrent ischemic Events (study) OASIS=Organization to Assess
Strategies for Ischemic Syndromes (study)
Reproduced with permission from Eikelboom JW et al Circulation 2006114774-782
Major Bleeding During First 30 Days Is Associated With Mortality Meta-analysis of 34146
ACS patients from the randomized OASIS OASIS-2 and CURE trials assessed the
association between bleeding within the first 30 days and death
Without major bleeding
With major bleeding
Days
Mo
rtality
(
)
Days from randomization
0 30 60 90 120 150 180 210 240 270 300 330 360 390
0
5
15
30
10
25
20
Major bleed only (without MI) (n=551)
Both MI and major bleed (n=94)
No MI or major bleed (n=12557)
MI only (without major bleed) (n=611)
Data on file The Medicines Company Parsippany NJ
289
125
86
34
Univariate analysis of 13819 patients from ACUITY
Impact of Non-CABG Major Bleeding and
MI at 30 Days on 1-Year Mortality
Radial Access 798 pts 62
Am Heart J 2009 Jan157(1)164-9 Epub 2008 Nov 6
Am Heart J 2009 Jan157(1)164-9 Epub 2008 Nov 6
Hypothetical mechanisms linking bleeding and mortality
Steg P G et al Eur Heart J 2011321854-
1864
Existing bleeding scores
bull TIMI Laboratory-based (hemoglobin hematocrit decrease)
bull GUSTO Clinical (severity)-based
bull GRACE Simplified laboratory and clinical
bull CURE Major minor (combined clin + lab)
bull ACUITY Major (intracranial-ocular access-site retroperit) lab
bull REPLACE-2 bull ISAR-REACT 3 bull PLATO bull STEEPLE bull CURRENT-OASIS
Thrombolysis conservative
PCI-based
BARC (Bleeding Academic Research Consortium) definitions
Mehran et al Circulation 20111232736-2747
bull Type 0 no evidence of bleeding bull Type 1 bleeding that is not actionable without
need for hospitalization or treatment (eg bruising hematoma nosebleeds etc)
bull Type 2 any clinically overt sign of hemorrhage that is actionable but does not meet criteria for type 3 4 or 5 Must meet at least 1 of following criteria ndash Requires intervention ndash Leads to hospitalization MANEJO MEDICO ndash Prompts evaluation
BARC (Bleeding Academic Research Consortium) definitions
Mehran et al Circulation 20111232736-2747
bull Type 3 clinical laboratory andor imaging evidence of bleeding with healthcare provider responses ndash BARC type 3a
bull any transfusion with overt bleeding bull overt bleeding plus hemoglobin drop ge3 to lt5 gdL
ndash BARC type 3b bull overt bleeding plus hemoglobin drop gt5 gdL bull Cardiac tamponade bull Bleeding requiring surgical intervention for control (excluding dentalnasalskinhemorrhoid) bull Bleeding requiring intravenous vasoactive drugs
ndash BARC type 3c bull Intracranial hemorrhage subcategories confirmed by autopsy
imaging or lumbar puncture bull Intraocular bleed compromising vision
BARC Bleeding Academic Research Consortium) definitions
Mehran et al Circulation 20111232736-2747
bull Type 4 Coronary Artery Bypass Graftndashrelated bleeding ndash Perioperative intracranial bleeding within 48 hours ndash Reoperation after closure of sternotomy for the purpose of controlling bleeding ndash Transfusion of ge5 U whole blood or packed red blood cells within a 48-hour period ndash Chest tube output 2 L within a 24-hour period
bull Type 5 ndash fatal bleeding bull Probable fatal bleeding (type 5a)
ndash bleeding that is clinically suspicious as the cause of death but the bleeding is not directly observed and there is no autopsy or confirmatory imaging
bull Definite fatal bleeding (type 5b) ndash bleeding that is directly observed (by either clinical specimen [blood
emesis stool etc] or imaging) or confirmed on autopsy
26 VCD
11
NSTEACS or STEMI with invasive management Aspirin+P2Y12 blocker
Trans-Femoral Access
Trans-Radial Access
To demonstrate that trans-radial intervention as
compared to femoral access site is associated to lower
rate of the composite endpoint of Death MI or Stroke
within the first 30 days
1deg co-Primary Objective
6 vs 42 βlt10 α 25 8200 patients
Adaptive study Design sample size (SS) will be increased
by the cross-over rate at 70 of planned SS
MATRIX Access site NCT01433627
MATRIX Access
39 93 132 200 276 380 490 685 857 1002 1190
1400 1684 1972 2248
2584 2926
3256 3560
3875 4144
4452 4726
5000 5322
5655 5896 6184
6458 6742 6982 7235 7444 7638 7844 8073
8404
Cumulative enrollment by month
8404
8404
8404 patients with ACS undergoing coronary angiography plusmn PCI from 11th Oct 2011 to 7th Nov 2014
Operator Eligibility Criteria Interventional cardiologist expertise in TRI and TFI including at least 75 transradial coronary interventions and at least 50 of interventions performed via radial route in the year preceding site initiation
Complete follow-up to 30 days available in 4183 (997) of radial and 4191 (99middot6) of femoral cohorts
Am Heart J 2014 Dec168(6)838-45e6
Cross Over and Procedural Success Rates
941 of radial and 974 of femoral cohorts received respective treatment as allocated
In 58 of radial and 23 of TF cohort the allocated access was attempted but failed
In 3 (01) in the radial and 13 (03) patients in the femoral groups the allocated access was not attempted
P=077 Plt0001
TIMI lt3 andor final stenosis gt30
88
103
15 significant reduction at nominal 5 alpha
which is however NOT significant at the pre-specificed
alpha of 25
Primary EP MACE
Femoral
Radial
Rate Ratio 083 95 CI 073 to 096 p=00092
117
98
NNTB 53 Femoral
Radial
Primary EP NACE
Mortalidad Total
IAM
Fatal and ST EPs All-Cause Cardiac non-CV mortality type of stent thrombosis
RR072
(053-099)
P=0045
RR 075
(054-104)
P=008 1
13
06
1
0
02
04
06
08
1
12
14
Radial Femoral
P=069
P=066
Mortality Stent Thrombosis
NNTB 167
Bleeding endpoints BARC TIMI GUSTO access vs non-access related
14
25
P=0013
RR 067 049-092
P=00004
RR 037 021-066
BARC 3 or 5
P=00098
RR 064 045-090
P=008
RR 072 050-104 P=020
RR 078 053-114
Major
or minor
moderate
or severe
P=082
P=068
Rardial Better Femoral Better 1
HAZARD RATIO (95 CI)
P-VALUES
Superiority Interaction
089 Intermediate (548-991)
075 (060-094)
104 (082-132) 076 0011
Centrersquos annual
volume of PCI
Low (247-544)
Intermediate (654-790)
Centrersquos
Proportion of
radial PCI
Low (149-644)
NSTE-ACS (tpndash) ACS type
STEMI
lt75 Age
ge75 023 088 (070-109)
082 (068-097) 0023 062
NACE Subgroup Analysis
High (1000-1950)
High (800-980)
NSTE-ACS (tp+)
Men Sex
Women
lt25 BMI
ge25
No
Ticagrelor or
prasugrel Yes
No Diabetes
Yes
lt60 GFR
ge60
No
History of
PVD Yes
2 025 050
075 (058-097) 0025
00048
101 (079-129)
095 (075 -122) 071
095
064 (051-080) lt0001
044
086 (068-108)
058 (033-103) 0059
019
085 (071-102) 007
0012 072 (056-093)
089 (076-105) 016 018
009 086 (073-102)
079 (063-099) 0038 053
007 083 (068-102)
084 (070-101) 006 094
045 091 (071-117)
080 (068-094) 008 043
001 078 (065-094)
086 (070-107) 018 051
060 091 (064-130)
083 (071-096) 0012 064
Radial Better Femoral Better 1
HAZARD RATIO (95 CI)
P-VALUES
Superiority Interaction
Intermediate (654-790)
Centrersquos
Proportion
of radial PCI
Low (149-644)
NSTE-ACS (tpndash) ACS
type
STEMI
Subgroup Analysis
High (800-980)
NSTE-ACS (tp+)
2
00157
128 (071-232)
069 (040 -119) 018
041
048 (028-081) 0006
010
087 (059-129) 049
049 (028-087) 0012
Intermediate (654-790) Centrersquos
Proportion
of radial PCI
Low (149-644)
NSTE-ACS (tpndash) ACS
type
STEMI
High (800-980)
NSTE-ACS (tp+)
020
090 (054-150)
057 (031 -103) 006
068
056 (032-097) 0035
054
062 (041-094)
166 (028-100) 058
0022
070 (042-117) 017
Mortality
Bleeding
4 050 025
1 2 050 025
Updated Meta-analysis 19328 ACS patients being randomly allocated to radial or femoral access
Rardial Better Femoral Better 1 4 025 050 2
Pre-Rival RIVAL Post-RIVAL MATRI
X Combined
Non-CABG
major bleeds
Death
myocardial
infarction or
stroke
Death
Myocardial
Infarction
Stroke
Pre-Rival RIVAL Post-RIVAL MATRI
X Combined
Pre-Rival RIVAL Post-RIVAL MATRI
X Combined
Pre-Rival RIVAL Post-RIVAL MATRI
X Combined
Pre-Rival RIVAL Post-RIVAL MATRI
X Combined
SUBGROUP Risk Ratio (95CI) P Value
Heterogenity
P Value I2
073 (043-123) 039 (023-067)
058 (046-072)
041 (022-076)
lt00001 0 05
1
067 (048-093) 086 (076-098) 086 (077-095)
098 (076-127)
00051 0 09
7
058 (039-087) 073 (053-099) 072 (060-088) 00011 0 10
0
085 (039-190) 091 (078-106) 091 (079-104)
092 (065-131)
01
6 0 08
8
068 (049-092)
082 (052-129)
077 (046-128) 086 (058-129)
073 (012-447)
140 (045-440) 100 (050-200) 105 (069-160)
143 (072-283)
08
0 0 07
5
026 (006-123)
Summary bull Among patients with an ACS with or without ST-segment
elevation who underwent invasive management the use
of radial access for coronary angiography plusmn PCI reduced
the rate of net adverse clinical events with a number
needed to treat for benefit of 53
ndash Differences between groups were driven by reductions in BARC
major bleeding unrelated to CABG and all-cause mortality with
radial access
bull Our results in conjunction with the updated meta-
analysis suggest that radial approach should
become the default access for patients with
ACS undergoing invasive management
Radial Acces 61000 menos Muertes
LA VIA TRANSRADIAL DEBERIA SER EL ACCESO DE ELECCION o ldquo DEFAULTrdquo PARA LOS PACIENTES CON SCA TRATADOS CON INTERVENCIONISMO PERCUTANEO
LA VIA TRANSRADIAL DEBERIA SER EL ACCESO DE ELECCION PARA TODO PACIENTE CONSIN SCA TRATADOS CON INTERVENCIONISMO PERCUTANEO
GRACIAS POR SU ATENCION
MACE
Mortality
No interaction between access and anticoagulant use in a post- hoc analysis of the subgroup of 7213 patients randomized to bivalirudin or unfractionated heparin for the two co-primary outcomes all-cause mortality or BARC 3 or 5 bleeding
Relevance of bleeding as a clinical endpoint
bull Availability of potent antithrombotic therapy including ndash ASA ndash P2Y12 inhibitors (clopidogrel prasugrel ticagrelor) ndash heparin ndash GP IIbIIIa inhibitors ndash direct thrombin inhibitors
bull has led to a reduction in ischemic events bull but is associated with an increased risk of
bleeding bull the increase in bleeding is associated with worse
clinical outcome
Rationale for a new bleeding definition
bull Increased importance of bleeding as prognostic factor
bull Need for assessment of bleeding in RCTs and registries
bull Lack of comparability bull Need for standardized definitions to avoid
erroneous conclusions
ndash regarding safety of a given agent ndash regarding superiority of one agent over another
Open questions regarding BARC
bull Why 48-hour window for CABG-related bleeding
bull Why type 1 bdquonot actionableldquo when patient may bdquotake actionldquo such as discontinuing medication (with potentially serious consequences such as ST)
bull Why consider intraocular bleed equivalent to intracranial bleed for BARC 3c
bull Type 1 bleed subject to misinterpretation by the patient
Hicks et al (editorial) Circulation 20111232664
Conclusion
bull BARC is a new objective hierarchically graded classification of bleeding
(Mehran Circulation [June 14] 20111232736)
bull BARC is based on consensus rather than data-driven
bull Prospective validation is warranted ndash across the spectrum of IHD
ndash across management strategies (conservative invasive)
ndash in the context of all invasive procedures (PCI CABG endovascular TAVI)
Conclusion (2)
bull Final validation of BARC and proof of its utility depend on
ndash its use by all future RCTs as common safety endpoint
ndash unanimous assessment procedure (questionnaires)
bull More important than using one or the other bleeding risk score is the agreement and commitment among clinical trialists to use the same score for comparability of data
bull All antithrombotic agents (except fondaparinux bivalirudin) are associated with increased bleeding risk
bull Aspirin and heparin reduce death MI at 30 days in NSTE-ACS
Choice of arterial access site and outcomes in patients with acute coronary
siacutendromes managed with an early invasive strategy the ACUITY trial Hamon M Rasmussen LH Manoukian SV Cequier A Lincoff MA Rupprecht HJ Gersh BJ Mann T Bertrand ME Mehran R Stone GW
AIMS The purpose of this study was to evaluate the impact of arterial access site on bleeding and ischaemic outcomes overall and by
treatment strategy in patients with acute coronary syndromes (ACS)
METHODS AND RESULTS In the ACUITY trial 13819 patients with moderate and high-risk ACS were randomised to either heparin
(unfractionated or enoxaparin) plus a glycoprotein IIbIIIa inhibitor (GPI) bivalirudin plus a GPI or bivalirudin alone
Per operator choice femoral access was utilised in 11989 patients (938) and radial Access in 798 patients (62) There was no significant
difference in composite ischaemia between the radial and femoral approaches at 30 days (81 vs 75 p=018) or 1 year (147 vs
155 p=077)although fewer major bleeding complications occurred with the use of radial access (30vs48 p=003) Use of
bivalirudin monotherapy was associated with significantly less 30-day major bleeding than heparin plus GPI after femoral access
(30 vs 58 plt00001) but not with radial access (42 vs 22 P=019)
Major or minor organ bleeding was reduced with bivalirudin monotherapy compared to heparin plus GPI to a similar extent with both
femoral (41 vs 74 Plt00001) and radial (49 vs 72 P=026) access
EuroIntervention 2009 May5(1)115-20
CONCLUSIONS
Transradial compared to femoral arterial access is associated with similar rates of composite ischaemia
anwith fewer major bleeding complications in patients with ACS managed invasively
Bivalirudin monotherapy compared to heparin plus GPIs significantly reduces
access site related major bleeding complications with femoral
but not radial artery access though non-access site related bleeding is reduced by
bivalirudin monotherapy in all patients
0 5 10 15 20 25 30
0
20
40
60
80
100
120
140
Mo
rta
lity
(
)
CURE=Clopidogrel in Unstable angina to prevent Recurrent ischemic Events (study) OASIS=Organization to Assess
Strategies for Ischemic Syndromes (study)
Reproduced with permission from Eikelboom JW et al Circulation 2006114774-782
Major Bleeding During First 30 Days Is Associated With Mortality Meta-analysis of 34146
ACS patients from the randomized OASIS OASIS-2 and CURE trials assessed the
association between bleeding within the first 30 days and death
Without major bleeding
With major bleeding
Days
Mo
rtality
(
)
Days from randomization
0 30 60 90 120 150 180 210 240 270 300 330 360 390
0
5
15
30
10
25
20
Major bleed only (without MI) (n=551)
Both MI and major bleed (n=94)
No MI or major bleed (n=12557)
MI only (without major bleed) (n=611)
Data on file The Medicines Company Parsippany NJ
289
125
86
34
Univariate analysis of 13819 patients from ACUITY
Impact of Non-CABG Major Bleeding and
MI at 30 Days on 1-Year Mortality
Radial Access 798 pts 62
Am Heart J 2009 Jan157(1)164-9 Epub 2008 Nov 6
Am Heart J 2009 Jan157(1)164-9 Epub 2008 Nov 6
Hypothetical mechanisms linking bleeding and mortality
Steg P G et al Eur Heart J 2011321854-
1864
Existing bleeding scores
bull TIMI Laboratory-based (hemoglobin hematocrit decrease)
bull GUSTO Clinical (severity)-based
bull GRACE Simplified laboratory and clinical
bull CURE Major minor (combined clin + lab)
bull ACUITY Major (intracranial-ocular access-site retroperit) lab
bull REPLACE-2 bull ISAR-REACT 3 bull PLATO bull STEEPLE bull CURRENT-OASIS
Thrombolysis conservative
PCI-based
BARC (Bleeding Academic Research Consortium) definitions
Mehran et al Circulation 20111232736-2747
bull Type 0 no evidence of bleeding bull Type 1 bleeding that is not actionable without
need for hospitalization or treatment (eg bruising hematoma nosebleeds etc)
bull Type 2 any clinically overt sign of hemorrhage that is actionable but does not meet criteria for type 3 4 or 5 Must meet at least 1 of following criteria ndash Requires intervention ndash Leads to hospitalization MANEJO MEDICO ndash Prompts evaluation
BARC (Bleeding Academic Research Consortium) definitions
Mehran et al Circulation 20111232736-2747
bull Type 3 clinical laboratory andor imaging evidence of bleeding with healthcare provider responses ndash BARC type 3a
bull any transfusion with overt bleeding bull overt bleeding plus hemoglobin drop ge3 to lt5 gdL
ndash BARC type 3b bull overt bleeding plus hemoglobin drop gt5 gdL bull Cardiac tamponade bull Bleeding requiring surgical intervention for control (excluding dentalnasalskinhemorrhoid) bull Bleeding requiring intravenous vasoactive drugs
ndash BARC type 3c bull Intracranial hemorrhage subcategories confirmed by autopsy
imaging or lumbar puncture bull Intraocular bleed compromising vision
BARC Bleeding Academic Research Consortium) definitions
Mehran et al Circulation 20111232736-2747
bull Type 4 Coronary Artery Bypass Graftndashrelated bleeding ndash Perioperative intracranial bleeding within 48 hours ndash Reoperation after closure of sternotomy for the purpose of controlling bleeding ndash Transfusion of ge5 U whole blood or packed red blood cells within a 48-hour period ndash Chest tube output 2 L within a 24-hour period
bull Type 5 ndash fatal bleeding bull Probable fatal bleeding (type 5a)
ndash bleeding that is clinically suspicious as the cause of death but the bleeding is not directly observed and there is no autopsy or confirmatory imaging
bull Definite fatal bleeding (type 5b) ndash bleeding that is directly observed (by either clinical specimen [blood
emesis stool etc] or imaging) or confirmed on autopsy
26 VCD
11
NSTEACS or STEMI with invasive management Aspirin+P2Y12 blocker
Trans-Femoral Access
Trans-Radial Access
To demonstrate that trans-radial intervention as
compared to femoral access site is associated to lower
rate of the composite endpoint of Death MI or Stroke
within the first 30 days
1deg co-Primary Objective
6 vs 42 βlt10 α 25 8200 patients
Adaptive study Design sample size (SS) will be increased
by the cross-over rate at 70 of planned SS
MATRIX Access site NCT01433627
MATRIX Access
39 93 132 200 276 380 490 685 857 1002 1190
1400 1684 1972 2248
2584 2926
3256 3560
3875 4144
4452 4726
5000 5322
5655 5896 6184
6458 6742 6982 7235 7444 7638 7844 8073
8404
Cumulative enrollment by month
8404
8404
8404 patients with ACS undergoing coronary angiography plusmn PCI from 11th Oct 2011 to 7th Nov 2014
Operator Eligibility Criteria Interventional cardiologist expertise in TRI and TFI including at least 75 transradial coronary interventions and at least 50 of interventions performed via radial route in the year preceding site initiation
Complete follow-up to 30 days available in 4183 (997) of radial and 4191 (99middot6) of femoral cohorts
Am Heart J 2014 Dec168(6)838-45e6
Cross Over and Procedural Success Rates
941 of radial and 974 of femoral cohorts received respective treatment as allocated
In 58 of radial and 23 of TF cohort the allocated access was attempted but failed
In 3 (01) in the radial and 13 (03) patients in the femoral groups the allocated access was not attempted
P=077 Plt0001
TIMI lt3 andor final stenosis gt30
88
103
15 significant reduction at nominal 5 alpha
which is however NOT significant at the pre-specificed
alpha of 25
Primary EP MACE
Femoral
Radial
Rate Ratio 083 95 CI 073 to 096 p=00092
117
98
NNTB 53 Femoral
Radial
Primary EP NACE
Mortalidad Total
IAM
Fatal and ST EPs All-Cause Cardiac non-CV mortality type of stent thrombosis
RR072
(053-099)
P=0045
RR 075
(054-104)
P=008 1
13
06
1
0
02
04
06
08
1
12
14
Radial Femoral
P=069
P=066
Mortality Stent Thrombosis
NNTB 167
Bleeding endpoints BARC TIMI GUSTO access vs non-access related
14
25
P=0013
RR 067 049-092
P=00004
RR 037 021-066
BARC 3 or 5
P=00098
RR 064 045-090
P=008
RR 072 050-104 P=020
RR 078 053-114
Major
or minor
moderate
or severe
P=082
P=068
Rardial Better Femoral Better 1
HAZARD RATIO (95 CI)
P-VALUES
Superiority Interaction
089 Intermediate (548-991)
075 (060-094)
104 (082-132) 076 0011
Centrersquos annual
volume of PCI
Low (247-544)
Intermediate (654-790)
Centrersquos
Proportion of
radial PCI
Low (149-644)
NSTE-ACS (tpndash) ACS type
STEMI
lt75 Age
ge75 023 088 (070-109)
082 (068-097) 0023 062
NACE Subgroup Analysis
High (1000-1950)
High (800-980)
NSTE-ACS (tp+)
Men Sex
Women
lt25 BMI
ge25
No
Ticagrelor or
prasugrel Yes
No Diabetes
Yes
lt60 GFR
ge60
No
History of
PVD Yes
2 025 050
075 (058-097) 0025
00048
101 (079-129)
095 (075 -122) 071
095
064 (051-080) lt0001
044
086 (068-108)
058 (033-103) 0059
019
085 (071-102) 007
0012 072 (056-093)
089 (076-105) 016 018
009 086 (073-102)
079 (063-099) 0038 053
007 083 (068-102)
084 (070-101) 006 094
045 091 (071-117)
080 (068-094) 008 043
001 078 (065-094)
086 (070-107) 018 051
060 091 (064-130)
083 (071-096) 0012 064
Radial Better Femoral Better 1
HAZARD RATIO (95 CI)
P-VALUES
Superiority Interaction
Intermediate (654-790)
Centrersquos
Proportion
of radial PCI
Low (149-644)
NSTE-ACS (tpndash) ACS
type
STEMI
Subgroup Analysis
High (800-980)
NSTE-ACS (tp+)
2
00157
128 (071-232)
069 (040 -119) 018
041
048 (028-081) 0006
010
087 (059-129) 049
049 (028-087) 0012
Intermediate (654-790) Centrersquos
Proportion
of radial PCI
Low (149-644)
NSTE-ACS (tpndash) ACS
type
STEMI
High (800-980)
NSTE-ACS (tp+)
020
090 (054-150)
057 (031 -103) 006
068
056 (032-097) 0035
054
062 (041-094)
166 (028-100) 058
0022
070 (042-117) 017
Mortality
Bleeding
4 050 025
1 2 050 025
Updated Meta-analysis 19328 ACS patients being randomly allocated to radial or femoral access
Rardial Better Femoral Better 1 4 025 050 2
Pre-Rival RIVAL Post-RIVAL MATRI
X Combined
Non-CABG
major bleeds
Death
myocardial
infarction or
stroke
Death
Myocardial
Infarction
Stroke
Pre-Rival RIVAL Post-RIVAL MATRI
X Combined
Pre-Rival RIVAL Post-RIVAL MATRI
X Combined
Pre-Rival RIVAL Post-RIVAL MATRI
X Combined
Pre-Rival RIVAL Post-RIVAL MATRI
X Combined
SUBGROUP Risk Ratio (95CI) P Value
Heterogenity
P Value I2
073 (043-123) 039 (023-067)
058 (046-072)
041 (022-076)
lt00001 0 05
1
067 (048-093) 086 (076-098) 086 (077-095)
098 (076-127)
00051 0 09
7
058 (039-087) 073 (053-099) 072 (060-088) 00011 0 10
0
085 (039-190) 091 (078-106) 091 (079-104)
092 (065-131)
01
6 0 08
8
068 (049-092)
082 (052-129)
077 (046-128) 086 (058-129)
073 (012-447)
140 (045-440) 100 (050-200) 105 (069-160)
143 (072-283)
08
0 0 07
5
026 (006-123)
Summary bull Among patients with an ACS with or without ST-segment
elevation who underwent invasive management the use
of radial access for coronary angiography plusmn PCI reduced
the rate of net adverse clinical events with a number
needed to treat for benefit of 53
ndash Differences between groups were driven by reductions in BARC
major bleeding unrelated to CABG and all-cause mortality with
radial access
bull Our results in conjunction with the updated meta-
analysis suggest that radial approach should
become the default access for patients with
ACS undergoing invasive management
Radial Acces 61000 menos Muertes
LA VIA TRANSRADIAL DEBERIA SER EL ACCESO DE ELECCION o ldquo DEFAULTrdquo PARA LOS PACIENTES CON SCA TRATADOS CON INTERVENCIONISMO PERCUTANEO
LA VIA TRANSRADIAL DEBERIA SER EL ACCESO DE ELECCION PARA TODO PACIENTE CONSIN SCA TRATADOS CON INTERVENCIONISMO PERCUTANEO
GRACIAS POR SU ATENCION
MACE
Mortality
No interaction between access and anticoagulant use in a post- hoc analysis of the subgroup of 7213 patients randomized to bivalirudin or unfractionated heparin for the two co-primary outcomes all-cause mortality or BARC 3 or 5 bleeding
Relevance of bleeding as a clinical endpoint
bull Availability of potent antithrombotic therapy including ndash ASA ndash P2Y12 inhibitors (clopidogrel prasugrel ticagrelor) ndash heparin ndash GP IIbIIIa inhibitors ndash direct thrombin inhibitors
bull has led to a reduction in ischemic events bull but is associated with an increased risk of
bleeding bull the increase in bleeding is associated with worse
clinical outcome
Rationale for a new bleeding definition
bull Increased importance of bleeding as prognostic factor
bull Need for assessment of bleeding in RCTs and registries
bull Lack of comparability bull Need for standardized definitions to avoid
erroneous conclusions
ndash regarding safety of a given agent ndash regarding superiority of one agent over another
Open questions regarding BARC
bull Why 48-hour window for CABG-related bleeding
bull Why type 1 bdquonot actionableldquo when patient may bdquotake actionldquo such as discontinuing medication (with potentially serious consequences such as ST)
bull Why consider intraocular bleed equivalent to intracranial bleed for BARC 3c
bull Type 1 bleed subject to misinterpretation by the patient
Hicks et al (editorial) Circulation 20111232664
Conclusion
bull BARC is a new objective hierarchically graded classification of bleeding
(Mehran Circulation [June 14] 20111232736)
bull BARC is based on consensus rather than data-driven
bull Prospective validation is warranted ndash across the spectrum of IHD
ndash across management strategies (conservative invasive)
ndash in the context of all invasive procedures (PCI CABG endovascular TAVI)
Conclusion (2)
bull Final validation of BARC and proof of its utility depend on
ndash its use by all future RCTs as common safety endpoint
ndash unanimous assessment procedure (questionnaires)
bull More important than using one or the other bleeding risk score is the agreement and commitment among clinical trialists to use the same score for comparability of data
Choice of arterial access site and outcomes in patients with acute coronary
siacutendromes managed with an early invasive strategy the ACUITY trial Hamon M Rasmussen LH Manoukian SV Cequier A Lincoff MA Rupprecht HJ Gersh BJ Mann T Bertrand ME Mehran R Stone GW
AIMS The purpose of this study was to evaluate the impact of arterial access site on bleeding and ischaemic outcomes overall and by
treatment strategy in patients with acute coronary syndromes (ACS)
METHODS AND RESULTS In the ACUITY trial 13819 patients with moderate and high-risk ACS were randomised to either heparin
(unfractionated or enoxaparin) plus a glycoprotein IIbIIIa inhibitor (GPI) bivalirudin plus a GPI or bivalirudin alone
Per operator choice femoral access was utilised in 11989 patients (938) and radial Access in 798 patients (62) There was no significant
difference in composite ischaemia between the radial and femoral approaches at 30 days (81 vs 75 p=018) or 1 year (147 vs
155 p=077)although fewer major bleeding complications occurred with the use of radial access (30vs48 p=003) Use of
bivalirudin monotherapy was associated with significantly less 30-day major bleeding than heparin plus GPI after femoral access
(30 vs 58 plt00001) but not with radial access (42 vs 22 P=019)
Major or minor organ bleeding was reduced with bivalirudin monotherapy compared to heparin plus GPI to a similar extent with both
femoral (41 vs 74 Plt00001) and radial (49 vs 72 P=026) access
EuroIntervention 2009 May5(1)115-20
CONCLUSIONS
Transradial compared to femoral arterial access is associated with similar rates of composite ischaemia
anwith fewer major bleeding complications in patients with ACS managed invasively
Bivalirudin monotherapy compared to heparin plus GPIs significantly reduces
access site related major bleeding complications with femoral
but not radial artery access though non-access site related bleeding is reduced by
bivalirudin monotherapy in all patients
0 5 10 15 20 25 30
0
20
40
60
80
100
120
140
Mo
rta
lity
(
)
CURE=Clopidogrel in Unstable angina to prevent Recurrent ischemic Events (study) OASIS=Organization to Assess
Strategies for Ischemic Syndromes (study)
Reproduced with permission from Eikelboom JW et al Circulation 2006114774-782
Major Bleeding During First 30 Days Is Associated With Mortality Meta-analysis of 34146
ACS patients from the randomized OASIS OASIS-2 and CURE trials assessed the
association between bleeding within the first 30 days and death
Without major bleeding
With major bleeding
Days
Mo
rtality
(
)
Days from randomization
0 30 60 90 120 150 180 210 240 270 300 330 360 390
0
5
15
30
10
25
20
Major bleed only (without MI) (n=551)
Both MI and major bleed (n=94)
No MI or major bleed (n=12557)
MI only (without major bleed) (n=611)
Data on file The Medicines Company Parsippany NJ
289
125
86
34
Univariate analysis of 13819 patients from ACUITY
Impact of Non-CABG Major Bleeding and
MI at 30 Days on 1-Year Mortality
Radial Access 798 pts 62
Am Heart J 2009 Jan157(1)164-9 Epub 2008 Nov 6
Am Heart J 2009 Jan157(1)164-9 Epub 2008 Nov 6
Hypothetical mechanisms linking bleeding and mortality
Steg P G et al Eur Heart J 2011321854-
1864
Existing bleeding scores
bull TIMI Laboratory-based (hemoglobin hematocrit decrease)
bull GUSTO Clinical (severity)-based
bull GRACE Simplified laboratory and clinical
bull CURE Major minor (combined clin + lab)
bull ACUITY Major (intracranial-ocular access-site retroperit) lab
bull REPLACE-2 bull ISAR-REACT 3 bull PLATO bull STEEPLE bull CURRENT-OASIS
Thrombolysis conservative
PCI-based
BARC (Bleeding Academic Research Consortium) definitions
Mehran et al Circulation 20111232736-2747
bull Type 0 no evidence of bleeding bull Type 1 bleeding that is not actionable without
need for hospitalization or treatment (eg bruising hematoma nosebleeds etc)
bull Type 2 any clinically overt sign of hemorrhage that is actionable but does not meet criteria for type 3 4 or 5 Must meet at least 1 of following criteria ndash Requires intervention ndash Leads to hospitalization MANEJO MEDICO ndash Prompts evaluation
BARC (Bleeding Academic Research Consortium) definitions
Mehran et al Circulation 20111232736-2747
bull Type 3 clinical laboratory andor imaging evidence of bleeding with healthcare provider responses ndash BARC type 3a
bull any transfusion with overt bleeding bull overt bleeding plus hemoglobin drop ge3 to lt5 gdL
ndash BARC type 3b bull overt bleeding plus hemoglobin drop gt5 gdL bull Cardiac tamponade bull Bleeding requiring surgical intervention for control (excluding dentalnasalskinhemorrhoid) bull Bleeding requiring intravenous vasoactive drugs
ndash BARC type 3c bull Intracranial hemorrhage subcategories confirmed by autopsy
imaging or lumbar puncture bull Intraocular bleed compromising vision
BARC Bleeding Academic Research Consortium) definitions
Mehran et al Circulation 20111232736-2747
bull Type 4 Coronary Artery Bypass Graftndashrelated bleeding ndash Perioperative intracranial bleeding within 48 hours ndash Reoperation after closure of sternotomy for the purpose of controlling bleeding ndash Transfusion of ge5 U whole blood or packed red blood cells within a 48-hour period ndash Chest tube output 2 L within a 24-hour period
bull Type 5 ndash fatal bleeding bull Probable fatal bleeding (type 5a)
ndash bleeding that is clinically suspicious as the cause of death but the bleeding is not directly observed and there is no autopsy or confirmatory imaging
bull Definite fatal bleeding (type 5b) ndash bleeding that is directly observed (by either clinical specimen [blood
emesis stool etc] or imaging) or confirmed on autopsy
26 VCD
11
NSTEACS or STEMI with invasive management Aspirin+P2Y12 blocker
Trans-Femoral Access
Trans-Radial Access
To demonstrate that trans-radial intervention as
compared to femoral access site is associated to lower
rate of the composite endpoint of Death MI or Stroke
within the first 30 days
1deg co-Primary Objective
6 vs 42 βlt10 α 25 8200 patients
Adaptive study Design sample size (SS) will be increased
by the cross-over rate at 70 of planned SS
MATRIX Access site NCT01433627
MATRIX Access
39 93 132 200 276 380 490 685 857 1002 1190
1400 1684 1972 2248
2584 2926
3256 3560
3875 4144
4452 4726
5000 5322
5655 5896 6184
6458 6742 6982 7235 7444 7638 7844 8073
8404
Cumulative enrollment by month
8404
8404
8404 patients with ACS undergoing coronary angiography plusmn PCI from 11th Oct 2011 to 7th Nov 2014
Operator Eligibility Criteria Interventional cardiologist expertise in TRI and TFI including at least 75 transradial coronary interventions and at least 50 of interventions performed via radial route in the year preceding site initiation
Complete follow-up to 30 days available in 4183 (997) of radial and 4191 (99middot6) of femoral cohorts
Am Heart J 2014 Dec168(6)838-45e6
Cross Over and Procedural Success Rates
941 of radial and 974 of femoral cohorts received respective treatment as allocated
In 58 of radial and 23 of TF cohort the allocated access was attempted but failed
In 3 (01) in the radial and 13 (03) patients in the femoral groups the allocated access was not attempted
P=077 Plt0001
TIMI lt3 andor final stenosis gt30
88
103
15 significant reduction at nominal 5 alpha
which is however NOT significant at the pre-specificed
alpha of 25
Primary EP MACE
Femoral
Radial
Rate Ratio 083 95 CI 073 to 096 p=00092
117
98
NNTB 53 Femoral
Radial
Primary EP NACE
Mortalidad Total
IAM
Fatal and ST EPs All-Cause Cardiac non-CV mortality type of stent thrombosis
RR072
(053-099)
P=0045
RR 075
(054-104)
P=008 1
13
06
1
0
02
04
06
08
1
12
14
Radial Femoral
P=069
P=066
Mortality Stent Thrombosis
NNTB 167
Bleeding endpoints BARC TIMI GUSTO access vs non-access related
14
25
P=0013
RR 067 049-092
P=00004
RR 037 021-066
BARC 3 or 5
P=00098
RR 064 045-090
P=008
RR 072 050-104 P=020
RR 078 053-114
Major
or minor
moderate
or severe
P=082
P=068
Rardial Better Femoral Better 1
HAZARD RATIO (95 CI)
P-VALUES
Superiority Interaction
089 Intermediate (548-991)
075 (060-094)
104 (082-132) 076 0011
Centrersquos annual
volume of PCI
Low (247-544)
Intermediate (654-790)
Centrersquos
Proportion of
radial PCI
Low (149-644)
NSTE-ACS (tpndash) ACS type
STEMI
lt75 Age
ge75 023 088 (070-109)
082 (068-097) 0023 062
NACE Subgroup Analysis
High (1000-1950)
High (800-980)
NSTE-ACS (tp+)
Men Sex
Women
lt25 BMI
ge25
No
Ticagrelor or
prasugrel Yes
No Diabetes
Yes
lt60 GFR
ge60
No
History of
PVD Yes
2 025 050
075 (058-097) 0025
00048
101 (079-129)
095 (075 -122) 071
095
064 (051-080) lt0001
044
086 (068-108)
058 (033-103) 0059
019
085 (071-102) 007
0012 072 (056-093)
089 (076-105) 016 018
009 086 (073-102)
079 (063-099) 0038 053
007 083 (068-102)
084 (070-101) 006 094
045 091 (071-117)
080 (068-094) 008 043
001 078 (065-094)
086 (070-107) 018 051
060 091 (064-130)
083 (071-096) 0012 064
Radial Better Femoral Better 1
HAZARD RATIO (95 CI)
P-VALUES
Superiority Interaction
Intermediate (654-790)
Centrersquos
Proportion
of radial PCI
Low (149-644)
NSTE-ACS (tpndash) ACS
type
STEMI
Subgroup Analysis
High (800-980)
NSTE-ACS (tp+)
2
00157
128 (071-232)
069 (040 -119) 018
041
048 (028-081) 0006
010
087 (059-129) 049
049 (028-087) 0012
Intermediate (654-790) Centrersquos
Proportion
of radial PCI
Low (149-644)
NSTE-ACS (tpndash) ACS
type
STEMI
High (800-980)
NSTE-ACS (tp+)
020
090 (054-150)
057 (031 -103) 006
068
056 (032-097) 0035
054
062 (041-094)
166 (028-100) 058
0022
070 (042-117) 017
Mortality
Bleeding
4 050 025
1 2 050 025
Updated Meta-analysis 19328 ACS patients being randomly allocated to radial or femoral access
Rardial Better Femoral Better 1 4 025 050 2
Pre-Rival RIVAL Post-RIVAL MATRI
X Combined
Non-CABG
major bleeds
Death
myocardial
infarction or
stroke
Death
Myocardial
Infarction
Stroke
Pre-Rival RIVAL Post-RIVAL MATRI
X Combined
Pre-Rival RIVAL Post-RIVAL MATRI
X Combined
Pre-Rival RIVAL Post-RIVAL MATRI
X Combined
Pre-Rival RIVAL Post-RIVAL MATRI
X Combined
SUBGROUP Risk Ratio (95CI) P Value
Heterogenity
P Value I2
073 (043-123) 039 (023-067)
058 (046-072)
041 (022-076)
lt00001 0 05
1
067 (048-093) 086 (076-098) 086 (077-095)
098 (076-127)
00051 0 09
7
058 (039-087) 073 (053-099) 072 (060-088) 00011 0 10
0
085 (039-190) 091 (078-106) 091 (079-104)
092 (065-131)
01
6 0 08
8
068 (049-092)
082 (052-129)
077 (046-128) 086 (058-129)
073 (012-447)
140 (045-440) 100 (050-200) 105 (069-160)
143 (072-283)
08
0 0 07
5
026 (006-123)
Summary bull Among patients with an ACS with or without ST-segment
elevation who underwent invasive management the use
of radial access for coronary angiography plusmn PCI reduced
the rate of net adverse clinical events with a number
needed to treat for benefit of 53
ndash Differences between groups were driven by reductions in BARC
major bleeding unrelated to CABG and all-cause mortality with
radial access
bull Our results in conjunction with the updated meta-
analysis suggest that radial approach should
become the default access for patients with
ACS undergoing invasive management
Radial Acces 61000 menos Muertes
LA VIA TRANSRADIAL DEBERIA SER EL ACCESO DE ELECCION o ldquo DEFAULTrdquo PARA LOS PACIENTES CON SCA TRATADOS CON INTERVENCIONISMO PERCUTANEO
LA VIA TRANSRADIAL DEBERIA SER EL ACCESO DE ELECCION PARA TODO PACIENTE CONSIN SCA TRATADOS CON INTERVENCIONISMO PERCUTANEO
GRACIAS POR SU ATENCION
MACE
Mortality
No interaction between access and anticoagulant use in a post- hoc analysis of the subgroup of 7213 patients randomized to bivalirudin or unfractionated heparin for the two co-primary outcomes all-cause mortality or BARC 3 or 5 bleeding
Relevance of bleeding as a clinical endpoint
bull Availability of potent antithrombotic therapy including ndash ASA ndash P2Y12 inhibitors (clopidogrel prasugrel ticagrelor) ndash heparin ndash GP IIbIIIa inhibitors ndash direct thrombin inhibitors
bull has led to a reduction in ischemic events bull but is associated with an increased risk of
bleeding bull the increase in bleeding is associated with worse
clinical outcome
Rationale for a new bleeding definition
bull Increased importance of bleeding as prognostic factor
bull Need for assessment of bleeding in RCTs and registries
bull Lack of comparability bull Need for standardized definitions to avoid
erroneous conclusions
ndash regarding safety of a given agent ndash regarding superiority of one agent over another
Open questions regarding BARC
bull Why 48-hour window for CABG-related bleeding
bull Why type 1 bdquonot actionableldquo when patient may bdquotake actionldquo such as discontinuing medication (with potentially serious consequences such as ST)
bull Why consider intraocular bleed equivalent to intracranial bleed for BARC 3c
bull Type 1 bleed subject to misinterpretation by the patient
Hicks et al (editorial) Circulation 20111232664
Conclusion
bull BARC is a new objective hierarchically graded classification of bleeding
(Mehran Circulation [June 14] 20111232736)
bull BARC is based on consensus rather than data-driven
bull Prospective validation is warranted ndash across the spectrum of IHD
ndash across management strategies (conservative invasive)
ndash in the context of all invasive procedures (PCI CABG endovascular TAVI)
Conclusion (2)
bull Final validation of BARC and proof of its utility depend on
ndash its use by all future RCTs as common safety endpoint
ndash unanimous assessment procedure (questionnaires)
bull More important than using one or the other bleeding risk score is the agreement and commitment among clinical trialists to use the same score for comparability of data
0 5 10 15 20 25 30
0
20
40
60
80
100
120
140
Mo
rta
lity
(
)
CURE=Clopidogrel in Unstable angina to prevent Recurrent ischemic Events (study) OASIS=Organization to Assess
Strategies for Ischemic Syndromes (study)
Reproduced with permission from Eikelboom JW et al Circulation 2006114774-782
Major Bleeding During First 30 Days Is Associated With Mortality Meta-analysis of 34146
ACS patients from the randomized OASIS OASIS-2 and CURE trials assessed the
association between bleeding within the first 30 days and death
Without major bleeding
With major bleeding
Days
Mo
rtality
(
)
Days from randomization
0 30 60 90 120 150 180 210 240 270 300 330 360 390
0
5
15
30
10
25
20
Major bleed only (without MI) (n=551)
Both MI and major bleed (n=94)
No MI or major bleed (n=12557)
MI only (without major bleed) (n=611)
Data on file The Medicines Company Parsippany NJ
289
125
86
34
Univariate analysis of 13819 patients from ACUITY
Impact of Non-CABG Major Bleeding and
MI at 30 Days on 1-Year Mortality
Radial Access 798 pts 62
Am Heart J 2009 Jan157(1)164-9 Epub 2008 Nov 6
Am Heart J 2009 Jan157(1)164-9 Epub 2008 Nov 6
Hypothetical mechanisms linking bleeding and mortality
Steg P G et al Eur Heart J 2011321854-
1864
Existing bleeding scores
bull TIMI Laboratory-based (hemoglobin hematocrit decrease)
bull GUSTO Clinical (severity)-based
bull GRACE Simplified laboratory and clinical
bull CURE Major minor (combined clin + lab)
bull ACUITY Major (intracranial-ocular access-site retroperit) lab
bull REPLACE-2 bull ISAR-REACT 3 bull PLATO bull STEEPLE bull CURRENT-OASIS
Thrombolysis conservative
PCI-based
BARC (Bleeding Academic Research Consortium) definitions
Mehran et al Circulation 20111232736-2747
bull Type 0 no evidence of bleeding bull Type 1 bleeding that is not actionable without
need for hospitalization or treatment (eg bruising hematoma nosebleeds etc)
bull Type 2 any clinically overt sign of hemorrhage that is actionable but does not meet criteria for type 3 4 or 5 Must meet at least 1 of following criteria ndash Requires intervention ndash Leads to hospitalization MANEJO MEDICO ndash Prompts evaluation
BARC (Bleeding Academic Research Consortium) definitions
Mehran et al Circulation 20111232736-2747
bull Type 3 clinical laboratory andor imaging evidence of bleeding with healthcare provider responses ndash BARC type 3a
bull any transfusion with overt bleeding bull overt bleeding plus hemoglobin drop ge3 to lt5 gdL
ndash BARC type 3b bull overt bleeding plus hemoglobin drop gt5 gdL bull Cardiac tamponade bull Bleeding requiring surgical intervention for control (excluding dentalnasalskinhemorrhoid) bull Bleeding requiring intravenous vasoactive drugs
ndash BARC type 3c bull Intracranial hemorrhage subcategories confirmed by autopsy
imaging or lumbar puncture bull Intraocular bleed compromising vision
BARC Bleeding Academic Research Consortium) definitions
Mehran et al Circulation 20111232736-2747
bull Type 4 Coronary Artery Bypass Graftndashrelated bleeding ndash Perioperative intracranial bleeding within 48 hours ndash Reoperation after closure of sternotomy for the purpose of controlling bleeding ndash Transfusion of ge5 U whole blood or packed red blood cells within a 48-hour period ndash Chest tube output 2 L within a 24-hour period
bull Type 5 ndash fatal bleeding bull Probable fatal bleeding (type 5a)
ndash bleeding that is clinically suspicious as the cause of death but the bleeding is not directly observed and there is no autopsy or confirmatory imaging
bull Definite fatal bleeding (type 5b) ndash bleeding that is directly observed (by either clinical specimen [blood
emesis stool etc] or imaging) or confirmed on autopsy
26 VCD
11
NSTEACS or STEMI with invasive management Aspirin+P2Y12 blocker
Trans-Femoral Access
Trans-Radial Access
To demonstrate that trans-radial intervention as
compared to femoral access site is associated to lower
rate of the composite endpoint of Death MI or Stroke
within the first 30 days
1deg co-Primary Objective
6 vs 42 βlt10 α 25 8200 patients
Adaptive study Design sample size (SS) will be increased
by the cross-over rate at 70 of planned SS
MATRIX Access site NCT01433627
MATRIX Access
39 93 132 200 276 380 490 685 857 1002 1190
1400 1684 1972 2248
2584 2926
3256 3560
3875 4144
4452 4726
5000 5322
5655 5896 6184
6458 6742 6982 7235 7444 7638 7844 8073
8404
Cumulative enrollment by month
8404
8404
8404 patients with ACS undergoing coronary angiography plusmn PCI from 11th Oct 2011 to 7th Nov 2014
Operator Eligibility Criteria Interventional cardiologist expertise in TRI and TFI including at least 75 transradial coronary interventions and at least 50 of interventions performed via radial route in the year preceding site initiation
Complete follow-up to 30 days available in 4183 (997) of radial and 4191 (99middot6) of femoral cohorts
Am Heart J 2014 Dec168(6)838-45e6
Cross Over and Procedural Success Rates
941 of radial and 974 of femoral cohorts received respective treatment as allocated
In 58 of radial and 23 of TF cohort the allocated access was attempted but failed
In 3 (01) in the radial and 13 (03) patients in the femoral groups the allocated access was not attempted
P=077 Plt0001
TIMI lt3 andor final stenosis gt30
88
103
15 significant reduction at nominal 5 alpha
which is however NOT significant at the pre-specificed
alpha of 25
Primary EP MACE
Femoral
Radial
Rate Ratio 083 95 CI 073 to 096 p=00092
117
98
NNTB 53 Femoral
Radial
Primary EP NACE
Mortalidad Total
IAM
Fatal and ST EPs All-Cause Cardiac non-CV mortality type of stent thrombosis
RR072
(053-099)
P=0045
RR 075
(054-104)
P=008 1
13
06
1
0
02
04
06
08
1
12
14
Radial Femoral
P=069
P=066
Mortality Stent Thrombosis
NNTB 167
Bleeding endpoints BARC TIMI GUSTO access vs non-access related
14
25
P=0013
RR 067 049-092
P=00004
RR 037 021-066
BARC 3 or 5
P=00098
RR 064 045-090
P=008
RR 072 050-104 P=020
RR 078 053-114
Major
or minor
moderate
or severe
P=082
P=068
Rardial Better Femoral Better 1
HAZARD RATIO (95 CI)
P-VALUES
Superiority Interaction
089 Intermediate (548-991)
075 (060-094)
104 (082-132) 076 0011
Centrersquos annual
volume of PCI
Low (247-544)
Intermediate (654-790)
Centrersquos
Proportion of
radial PCI
Low (149-644)
NSTE-ACS (tpndash) ACS type
STEMI
lt75 Age
ge75 023 088 (070-109)
082 (068-097) 0023 062
NACE Subgroup Analysis
High (1000-1950)
High (800-980)
NSTE-ACS (tp+)
Men Sex
Women
lt25 BMI
ge25
No
Ticagrelor or
prasugrel Yes
No Diabetes
Yes
lt60 GFR
ge60
No
History of
PVD Yes
2 025 050
075 (058-097) 0025
00048
101 (079-129)
095 (075 -122) 071
095
064 (051-080) lt0001
044
086 (068-108)
058 (033-103) 0059
019
085 (071-102) 007
0012 072 (056-093)
089 (076-105) 016 018
009 086 (073-102)
079 (063-099) 0038 053
007 083 (068-102)
084 (070-101) 006 094
045 091 (071-117)
080 (068-094) 008 043
001 078 (065-094)
086 (070-107) 018 051
060 091 (064-130)
083 (071-096) 0012 064
Radial Better Femoral Better 1
HAZARD RATIO (95 CI)
P-VALUES
Superiority Interaction
Intermediate (654-790)
Centrersquos
Proportion
of radial PCI
Low (149-644)
NSTE-ACS (tpndash) ACS
type
STEMI
Subgroup Analysis
High (800-980)
NSTE-ACS (tp+)
2
00157
128 (071-232)
069 (040 -119) 018
041
048 (028-081) 0006
010
087 (059-129) 049
049 (028-087) 0012
Intermediate (654-790) Centrersquos
Proportion
of radial PCI
Low (149-644)
NSTE-ACS (tpndash) ACS
type
STEMI
High (800-980)
NSTE-ACS (tp+)
020
090 (054-150)
057 (031 -103) 006
068
056 (032-097) 0035
054
062 (041-094)
166 (028-100) 058
0022
070 (042-117) 017
Mortality
Bleeding
4 050 025
1 2 050 025
Updated Meta-analysis 19328 ACS patients being randomly allocated to radial or femoral access
Rardial Better Femoral Better 1 4 025 050 2
Pre-Rival RIVAL Post-RIVAL MATRI
X Combined
Non-CABG
major bleeds
Death
myocardial
infarction or
stroke
Death
Myocardial
Infarction
Stroke
Pre-Rival RIVAL Post-RIVAL MATRI
X Combined
Pre-Rival RIVAL Post-RIVAL MATRI
X Combined
Pre-Rival RIVAL Post-RIVAL MATRI
X Combined
Pre-Rival RIVAL Post-RIVAL MATRI
X Combined
SUBGROUP Risk Ratio (95CI) P Value
Heterogenity
P Value I2
073 (043-123) 039 (023-067)
058 (046-072)
041 (022-076)
lt00001 0 05
1
067 (048-093) 086 (076-098) 086 (077-095)
098 (076-127)
00051 0 09
7
058 (039-087) 073 (053-099) 072 (060-088) 00011 0 10
0
085 (039-190) 091 (078-106) 091 (079-104)
092 (065-131)
01
6 0 08
8
068 (049-092)
082 (052-129)
077 (046-128) 086 (058-129)
073 (012-447)
140 (045-440) 100 (050-200) 105 (069-160)
143 (072-283)
08
0 0 07
5
026 (006-123)
Summary bull Among patients with an ACS with or without ST-segment
elevation who underwent invasive management the use
of radial access for coronary angiography plusmn PCI reduced
the rate of net adverse clinical events with a number
needed to treat for benefit of 53
ndash Differences between groups were driven by reductions in BARC
major bleeding unrelated to CABG and all-cause mortality with
radial access
bull Our results in conjunction with the updated meta-
analysis suggest that radial approach should
become the default access for patients with
ACS undergoing invasive management
Radial Acces 61000 menos Muertes
LA VIA TRANSRADIAL DEBERIA SER EL ACCESO DE ELECCION o ldquo DEFAULTrdquo PARA LOS PACIENTES CON SCA TRATADOS CON INTERVENCIONISMO PERCUTANEO
LA VIA TRANSRADIAL DEBERIA SER EL ACCESO DE ELECCION PARA TODO PACIENTE CONSIN SCA TRATADOS CON INTERVENCIONISMO PERCUTANEO
GRACIAS POR SU ATENCION
MACE
Mortality
No interaction between access and anticoagulant use in a post- hoc analysis of the subgroup of 7213 patients randomized to bivalirudin or unfractionated heparin for the two co-primary outcomes all-cause mortality or BARC 3 or 5 bleeding
Relevance of bleeding as a clinical endpoint
bull Availability of potent antithrombotic therapy including ndash ASA ndash P2Y12 inhibitors (clopidogrel prasugrel ticagrelor) ndash heparin ndash GP IIbIIIa inhibitors ndash direct thrombin inhibitors
bull has led to a reduction in ischemic events bull but is associated with an increased risk of
bleeding bull the increase in bleeding is associated with worse
clinical outcome
Rationale for a new bleeding definition
bull Increased importance of bleeding as prognostic factor
bull Need for assessment of bleeding in RCTs and registries
bull Lack of comparability bull Need for standardized definitions to avoid
erroneous conclusions
ndash regarding safety of a given agent ndash regarding superiority of one agent over another
Open questions regarding BARC
bull Why 48-hour window for CABG-related bleeding
bull Why type 1 bdquonot actionableldquo when patient may bdquotake actionldquo such as discontinuing medication (with potentially serious consequences such as ST)
bull Why consider intraocular bleed equivalent to intracranial bleed for BARC 3c
bull Type 1 bleed subject to misinterpretation by the patient
Hicks et al (editorial) Circulation 20111232664
Conclusion
bull BARC is a new objective hierarchically graded classification of bleeding
(Mehran Circulation [June 14] 20111232736)
bull BARC is based on consensus rather than data-driven
bull Prospective validation is warranted ndash across the spectrum of IHD
ndash across management strategies (conservative invasive)
ndash in the context of all invasive procedures (PCI CABG endovascular TAVI)
Conclusion (2)
bull Final validation of BARC and proof of its utility depend on
ndash its use by all future RCTs as common safety endpoint
ndash unanimous assessment procedure (questionnaires)
bull More important than using one or the other bleeding risk score is the agreement and commitment among clinical trialists to use the same score for comparability of data
Mo
rtality
(
)
Days from randomization
0 30 60 90 120 150 180 210 240 270 300 330 360 390
0
5
15
30
10
25
20
Major bleed only (without MI) (n=551)
Both MI and major bleed (n=94)
No MI or major bleed (n=12557)
MI only (without major bleed) (n=611)
Data on file The Medicines Company Parsippany NJ
289
125
86
34
Univariate analysis of 13819 patients from ACUITY
Impact of Non-CABG Major Bleeding and
MI at 30 Days on 1-Year Mortality
Radial Access 798 pts 62
Am Heart J 2009 Jan157(1)164-9 Epub 2008 Nov 6
Am Heart J 2009 Jan157(1)164-9 Epub 2008 Nov 6
Hypothetical mechanisms linking bleeding and mortality
Steg P G et al Eur Heart J 2011321854-
1864
Existing bleeding scores
bull TIMI Laboratory-based (hemoglobin hematocrit decrease)
bull GUSTO Clinical (severity)-based
bull GRACE Simplified laboratory and clinical
bull CURE Major minor (combined clin + lab)
bull ACUITY Major (intracranial-ocular access-site retroperit) lab
bull REPLACE-2 bull ISAR-REACT 3 bull PLATO bull STEEPLE bull CURRENT-OASIS
Thrombolysis conservative
PCI-based
BARC (Bleeding Academic Research Consortium) definitions
Mehran et al Circulation 20111232736-2747
bull Type 0 no evidence of bleeding bull Type 1 bleeding that is not actionable without
need for hospitalization or treatment (eg bruising hematoma nosebleeds etc)
bull Type 2 any clinically overt sign of hemorrhage that is actionable but does not meet criteria for type 3 4 or 5 Must meet at least 1 of following criteria ndash Requires intervention ndash Leads to hospitalization MANEJO MEDICO ndash Prompts evaluation
BARC (Bleeding Academic Research Consortium) definitions
Mehran et al Circulation 20111232736-2747
bull Type 3 clinical laboratory andor imaging evidence of bleeding with healthcare provider responses ndash BARC type 3a
bull any transfusion with overt bleeding bull overt bleeding plus hemoglobin drop ge3 to lt5 gdL
ndash BARC type 3b bull overt bleeding plus hemoglobin drop gt5 gdL bull Cardiac tamponade bull Bleeding requiring surgical intervention for control (excluding dentalnasalskinhemorrhoid) bull Bleeding requiring intravenous vasoactive drugs
ndash BARC type 3c bull Intracranial hemorrhage subcategories confirmed by autopsy
imaging or lumbar puncture bull Intraocular bleed compromising vision
BARC Bleeding Academic Research Consortium) definitions
Mehran et al Circulation 20111232736-2747
bull Type 4 Coronary Artery Bypass Graftndashrelated bleeding ndash Perioperative intracranial bleeding within 48 hours ndash Reoperation after closure of sternotomy for the purpose of controlling bleeding ndash Transfusion of ge5 U whole blood or packed red blood cells within a 48-hour period ndash Chest tube output 2 L within a 24-hour period
bull Type 5 ndash fatal bleeding bull Probable fatal bleeding (type 5a)
ndash bleeding that is clinically suspicious as the cause of death but the bleeding is not directly observed and there is no autopsy or confirmatory imaging
bull Definite fatal bleeding (type 5b) ndash bleeding that is directly observed (by either clinical specimen [blood
emesis stool etc] or imaging) or confirmed on autopsy
26 VCD
11
NSTEACS or STEMI with invasive management Aspirin+P2Y12 blocker
Trans-Femoral Access
Trans-Radial Access
To demonstrate that trans-radial intervention as
compared to femoral access site is associated to lower
rate of the composite endpoint of Death MI or Stroke
within the first 30 days
1deg co-Primary Objective
6 vs 42 βlt10 α 25 8200 patients
Adaptive study Design sample size (SS) will be increased
by the cross-over rate at 70 of planned SS
MATRIX Access site NCT01433627
MATRIX Access
39 93 132 200 276 380 490 685 857 1002 1190
1400 1684 1972 2248
2584 2926
3256 3560
3875 4144
4452 4726
5000 5322
5655 5896 6184
6458 6742 6982 7235 7444 7638 7844 8073
8404
Cumulative enrollment by month
8404
8404
8404 patients with ACS undergoing coronary angiography plusmn PCI from 11th Oct 2011 to 7th Nov 2014
Operator Eligibility Criteria Interventional cardiologist expertise in TRI and TFI including at least 75 transradial coronary interventions and at least 50 of interventions performed via radial route in the year preceding site initiation
Complete follow-up to 30 days available in 4183 (997) of radial and 4191 (99middot6) of femoral cohorts
Am Heart J 2014 Dec168(6)838-45e6
Cross Over and Procedural Success Rates
941 of radial and 974 of femoral cohorts received respective treatment as allocated
In 58 of radial and 23 of TF cohort the allocated access was attempted but failed
In 3 (01) in the radial and 13 (03) patients in the femoral groups the allocated access was not attempted
P=077 Plt0001
TIMI lt3 andor final stenosis gt30
88
103
15 significant reduction at nominal 5 alpha
which is however NOT significant at the pre-specificed
alpha of 25
Primary EP MACE
Femoral
Radial
Rate Ratio 083 95 CI 073 to 096 p=00092
117
98
NNTB 53 Femoral
Radial
Primary EP NACE
Mortalidad Total
IAM
Fatal and ST EPs All-Cause Cardiac non-CV mortality type of stent thrombosis
RR072
(053-099)
P=0045
RR 075
(054-104)
P=008 1
13
06
1
0
02
04
06
08
1
12
14
Radial Femoral
P=069
P=066
Mortality Stent Thrombosis
NNTB 167
Bleeding endpoints BARC TIMI GUSTO access vs non-access related
14
25
P=0013
RR 067 049-092
P=00004
RR 037 021-066
BARC 3 or 5
P=00098
RR 064 045-090
P=008
RR 072 050-104 P=020
RR 078 053-114
Major
or minor
moderate
or severe
P=082
P=068
Rardial Better Femoral Better 1
HAZARD RATIO (95 CI)
P-VALUES
Superiority Interaction
089 Intermediate (548-991)
075 (060-094)
104 (082-132) 076 0011
Centrersquos annual
volume of PCI
Low (247-544)
Intermediate (654-790)
Centrersquos
Proportion of
radial PCI
Low (149-644)
NSTE-ACS (tpndash) ACS type
STEMI
lt75 Age
ge75 023 088 (070-109)
082 (068-097) 0023 062
NACE Subgroup Analysis
High (1000-1950)
High (800-980)
NSTE-ACS (tp+)
Men Sex
Women
lt25 BMI
ge25
No
Ticagrelor or
prasugrel Yes
No Diabetes
Yes
lt60 GFR
ge60
No
History of
PVD Yes
2 025 050
075 (058-097) 0025
00048
101 (079-129)
095 (075 -122) 071
095
064 (051-080) lt0001
044
086 (068-108)
058 (033-103) 0059
019
085 (071-102) 007
0012 072 (056-093)
089 (076-105) 016 018
009 086 (073-102)
079 (063-099) 0038 053
007 083 (068-102)
084 (070-101) 006 094
045 091 (071-117)
080 (068-094) 008 043
001 078 (065-094)
086 (070-107) 018 051
060 091 (064-130)
083 (071-096) 0012 064
Radial Better Femoral Better 1
HAZARD RATIO (95 CI)
P-VALUES
Superiority Interaction
Intermediate (654-790)
Centrersquos
Proportion
of radial PCI
Low (149-644)
NSTE-ACS (tpndash) ACS
type
STEMI
Subgroup Analysis
High (800-980)
NSTE-ACS (tp+)
2
00157
128 (071-232)
069 (040 -119) 018
041
048 (028-081) 0006
010
087 (059-129) 049
049 (028-087) 0012
Intermediate (654-790) Centrersquos
Proportion
of radial PCI
Low (149-644)
NSTE-ACS (tpndash) ACS
type
STEMI
High (800-980)
NSTE-ACS (tp+)
020
090 (054-150)
057 (031 -103) 006
068
056 (032-097) 0035
054
062 (041-094)
166 (028-100) 058
0022
070 (042-117) 017
Mortality
Bleeding
4 050 025
1 2 050 025
Updated Meta-analysis 19328 ACS patients being randomly allocated to radial or femoral access
Rardial Better Femoral Better 1 4 025 050 2
Pre-Rival RIVAL Post-RIVAL MATRI
X Combined
Non-CABG
major bleeds
Death
myocardial
infarction or
stroke
Death
Myocardial
Infarction
Stroke
Pre-Rival RIVAL Post-RIVAL MATRI
X Combined
Pre-Rival RIVAL Post-RIVAL MATRI
X Combined
Pre-Rival RIVAL Post-RIVAL MATRI
X Combined
Pre-Rival RIVAL Post-RIVAL MATRI
X Combined
SUBGROUP Risk Ratio (95CI) P Value
Heterogenity
P Value I2
073 (043-123) 039 (023-067)
058 (046-072)
041 (022-076)
lt00001 0 05
1
067 (048-093) 086 (076-098) 086 (077-095)
098 (076-127)
00051 0 09
7
058 (039-087) 073 (053-099) 072 (060-088) 00011 0 10
0
085 (039-190) 091 (078-106) 091 (079-104)
092 (065-131)
01
6 0 08
8
068 (049-092)
082 (052-129)
077 (046-128) 086 (058-129)
073 (012-447)
140 (045-440) 100 (050-200) 105 (069-160)
143 (072-283)
08
0 0 07
5
026 (006-123)
Summary bull Among patients with an ACS with or without ST-segment
elevation who underwent invasive management the use
of radial access for coronary angiography plusmn PCI reduced
the rate of net adverse clinical events with a number
needed to treat for benefit of 53
ndash Differences between groups were driven by reductions in BARC
major bleeding unrelated to CABG and all-cause mortality with
radial access
bull Our results in conjunction with the updated meta-
analysis suggest that radial approach should
become the default access for patients with
ACS undergoing invasive management
Radial Acces 61000 menos Muertes
LA VIA TRANSRADIAL DEBERIA SER EL ACCESO DE ELECCION o ldquo DEFAULTrdquo PARA LOS PACIENTES CON SCA TRATADOS CON INTERVENCIONISMO PERCUTANEO
LA VIA TRANSRADIAL DEBERIA SER EL ACCESO DE ELECCION PARA TODO PACIENTE CONSIN SCA TRATADOS CON INTERVENCIONISMO PERCUTANEO
GRACIAS POR SU ATENCION
MACE
Mortality
No interaction between access and anticoagulant use in a post- hoc analysis of the subgroup of 7213 patients randomized to bivalirudin or unfractionated heparin for the two co-primary outcomes all-cause mortality or BARC 3 or 5 bleeding
Relevance of bleeding as a clinical endpoint
bull Availability of potent antithrombotic therapy including ndash ASA ndash P2Y12 inhibitors (clopidogrel prasugrel ticagrelor) ndash heparin ndash GP IIbIIIa inhibitors ndash direct thrombin inhibitors
bull has led to a reduction in ischemic events bull but is associated with an increased risk of
bleeding bull the increase in bleeding is associated with worse
clinical outcome
Rationale for a new bleeding definition
bull Increased importance of bleeding as prognostic factor
bull Need for assessment of bleeding in RCTs and registries
bull Lack of comparability bull Need for standardized definitions to avoid
erroneous conclusions
ndash regarding safety of a given agent ndash regarding superiority of one agent over another
Open questions regarding BARC
bull Why 48-hour window for CABG-related bleeding
bull Why type 1 bdquonot actionableldquo when patient may bdquotake actionldquo such as discontinuing medication (with potentially serious consequences such as ST)
bull Why consider intraocular bleed equivalent to intracranial bleed for BARC 3c
bull Type 1 bleed subject to misinterpretation by the patient
Hicks et al (editorial) Circulation 20111232664
Conclusion
bull BARC is a new objective hierarchically graded classification of bleeding
(Mehran Circulation [June 14] 20111232736)
bull BARC is based on consensus rather than data-driven
bull Prospective validation is warranted ndash across the spectrum of IHD
ndash across management strategies (conservative invasive)
ndash in the context of all invasive procedures (PCI CABG endovascular TAVI)
Conclusion (2)
bull Final validation of BARC and proof of its utility depend on
ndash its use by all future RCTs as common safety endpoint
ndash unanimous assessment procedure (questionnaires)
bull More important than using one or the other bleeding risk score is the agreement and commitment among clinical trialists to use the same score for comparability of data
Am Heart J 2009 Jan157(1)164-9 Epub 2008 Nov 6
Am Heart J 2009 Jan157(1)164-9 Epub 2008 Nov 6
Hypothetical mechanisms linking bleeding and mortality
Steg P G et al Eur Heart J 2011321854-
1864
Existing bleeding scores
bull TIMI Laboratory-based (hemoglobin hematocrit decrease)
bull GUSTO Clinical (severity)-based
bull GRACE Simplified laboratory and clinical
bull CURE Major minor (combined clin + lab)
bull ACUITY Major (intracranial-ocular access-site retroperit) lab
bull REPLACE-2 bull ISAR-REACT 3 bull PLATO bull STEEPLE bull CURRENT-OASIS
Thrombolysis conservative
PCI-based
BARC (Bleeding Academic Research Consortium) definitions
Mehran et al Circulation 20111232736-2747
bull Type 0 no evidence of bleeding bull Type 1 bleeding that is not actionable without
need for hospitalization or treatment (eg bruising hematoma nosebleeds etc)
bull Type 2 any clinically overt sign of hemorrhage that is actionable but does not meet criteria for type 3 4 or 5 Must meet at least 1 of following criteria ndash Requires intervention ndash Leads to hospitalization MANEJO MEDICO ndash Prompts evaluation
BARC (Bleeding Academic Research Consortium) definitions
Mehran et al Circulation 20111232736-2747
bull Type 3 clinical laboratory andor imaging evidence of bleeding with healthcare provider responses ndash BARC type 3a
bull any transfusion with overt bleeding bull overt bleeding plus hemoglobin drop ge3 to lt5 gdL
ndash BARC type 3b bull overt bleeding plus hemoglobin drop gt5 gdL bull Cardiac tamponade bull Bleeding requiring surgical intervention for control (excluding dentalnasalskinhemorrhoid) bull Bleeding requiring intravenous vasoactive drugs
ndash BARC type 3c bull Intracranial hemorrhage subcategories confirmed by autopsy
imaging or lumbar puncture bull Intraocular bleed compromising vision
BARC Bleeding Academic Research Consortium) definitions
Mehran et al Circulation 20111232736-2747
bull Type 4 Coronary Artery Bypass Graftndashrelated bleeding ndash Perioperative intracranial bleeding within 48 hours ndash Reoperation after closure of sternotomy for the purpose of controlling bleeding ndash Transfusion of ge5 U whole blood or packed red blood cells within a 48-hour period ndash Chest tube output 2 L within a 24-hour period
bull Type 5 ndash fatal bleeding bull Probable fatal bleeding (type 5a)
ndash bleeding that is clinically suspicious as the cause of death but the bleeding is not directly observed and there is no autopsy or confirmatory imaging
bull Definite fatal bleeding (type 5b) ndash bleeding that is directly observed (by either clinical specimen [blood
emesis stool etc] or imaging) or confirmed on autopsy
26 VCD
11
NSTEACS or STEMI with invasive management Aspirin+P2Y12 blocker
Trans-Femoral Access
Trans-Radial Access
To demonstrate that trans-radial intervention as
compared to femoral access site is associated to lower
rate of the composite endpoint of Death MI or Stroke
within the first 30 days
1deg co-Primary Objective
6 vs 42 βlt10 α 25 8200 patients
Adaptive study Design sample size (SS) will be increased
by the cross-over rate at 70 of planned SS
MATRIX Access site NCT01433627
MATRIX Access
39 93 132 200 276 380 490 685 857 1002 1190
1400 1684 1972 2248
2584 2926
3256 3560
3875 4144
4452 4726
5000 5322
5655 5896 6184
6458 6742 6982 7235 7444 7638 7844 8073
8404
Cumulative enrollment by month
8404
8404
8404 patients with ACS undergoing coronary angiography plusmn PCI from 11th Oct 2011 to 7th Nov 2014
Operator Eligibility Criteria Interventional cardiologist expertise in TRI and TFI including at least 75 transradial coronary interventions and at least 50 of interventions performed via radial route in the year preceding site initiation
Complete follow-up to 30 days available in 4183 (997) of radial and 4191 (99middot6) of femoral cohorts
Am Heart J 2014 Dec168(6)838-45e6
Cross Over and Procedural Success Rates
941 of radial and 974 of femoral cohorts received respective treatment as allocated
In 58 of radial and 23 of TF cohort the allocated access was attempted but failed
In 3 (01) in the radial and 13 (03) patients in the femoral groups the allocated access was not attempted
P=077 Plt0001
TIMI lt3 andor final stenosis gt30
88
103
15 significant reduction at nominal 5 alpha
which is however NOT significant at the pre-specificed
alpha of 25
Primary EP MACE
Femoral
Radial
Rate Ratio 083 95 CI 073 to 096 p=00092
117
98
NNTB 53 Femoral
Radial
Primary EP NACE
Mortalidad Total
IAM
Fatal and ST EPs All-Cause Cardiac non-CV mortality type of stent thrombosis
RR072
(053-099)
P=0045
RR 075
(054-104)
P=008 1
13
06
1
0
02
04
06
08
1
12
14
Radial Femoral
P=069
P=066
Mortality Stent Thrombosis
NNTB 167
Bleeding endpoints BARC TIMI GUSTO access vs non-access related
14
25
P=0013
RR 067 049-092
P=00004
RR 037 021-066
BARC 3 or 5
P=00098
RR 064 045-090
P=008
RR 072 050-104 P=020
RR 078 053-114
Major
or minor
moderate
or severe
P=082
P=068
Rardial Better Femoral Better 1
HAZARD RATIO (95 CI)
P-VALUES
Superiority Interaction
089 Intermediate (548-991)
075 (060-094)
104 (082-132) 076 0011
Centrersquos annual
volume of PCI
Low (247-544)
Intermediate (654-790)
Centrersquos
Proportion of
radial PCI
Low (149-644)
NSTE-ACS (tpndash) ACS type
STEMI
lt75 Age
ge75 023 088 (070-109)
082 (068-097) 0023 062
NACE Subgroup Analysis
High (1000-1950)
High (800-980)
NSTE-ACS (tp+)
Men Sex
Women
lt25 BMI
ge25
No
Ticagrelor or
prasugrel Yes
No Diabetes
Yes
lt60 GFR
ge60
No
History of
PVD Yes
2 025 050
075 (058-097) 0025
00048
101 (079-129)
095 (075 -122) 071
095
064 (051-080) lt0001
044
086 (068-108)
058 (033-103) 0059
019
085 (071-102) 007
0012 072 (056-093)
089 (076-105) 016 018
009 086 (073-102)
079 (063-099) 0038 053
007 083 (068-102)
084 (070-101) 006 094
045 091 (071-117)
080 (068-094) 008 043
001 078 (065-094)
086 (070-107) 018 051
060 091 (064-130)
083 (071-096) 0012 064
Radial Better Femoral Better 1
HAZARD RATIO (95 CI)
P-VALUES
Superiority Interaction
Intermediate (654-790)
Centrersquos
Proportion
of radial PCI
Low (149-644)
NSTE-ACS (tpndash) ACS
type
STEMI
Subgroup Analysis
High (800-980)
NSTE-ACS (tp+)
2
00157
128 (071-232)
069 (040 -119) 018
041
048 (028-081) 0006
010
087 (059-129) 049
049 (028-087) 0012
Intermediate (654-790) Centrersquos
Proportion
of radial PCI
Low (149-644)
NSTE-ACS (tpndash) ACS
type
STEMI
High (800-980)
NSTE-ACS (tp+)
020
090 (054-150)
057 (031 -103) 006
068
056 (032-097) 0035
054
062 (041-094)
166 (028-100) 058
0022
070 (042-117) 017
Mortality
Bleeding
4 050 025
1 2 050 025
Updated Meta-analysis 19328 ACS patients being randomly allocated to radial or femoral access
Rardial Better Femoral Better 1 4 025 050 2
Pre-Rival RIVAL Post-RIVAL MATRI
X Combined
Non-CABG
major bleeds
Death
myocardial
infarction or
stroke
Death
Myocardial
Infarction
Stroke
Pre-Rival RIVAL Post-RIVAL MATRI
X Combined
Pre-Rival RIVAL Post-RIVAL MATRI
X Combined
Pre-Rival RIVAL Post-RIVAL MATRI
X Combined
Pre-Rival RIVAL Post-RIVAL MATRI
X Combined
SUBGROUP Risk Ratio (95CI) P Value
Heterogenity
P Value I2
073 (043-123) 039 (023-067)
058 (046-072)
041 (022-076)
lt00001 0 05
1
067 (048-093) 086 (076-098) 086 (077-095)
098 (076-127)
00051 0 09
7
058 (039-087) 073 (053-099) 072 (060-088) 00011 0 10
0
085 (039-190) 091 (078-106) 091 (079-104)
092 (065-131)
01
6 0 08
8
068 (049-092)
082 (052-129)
077 (046-128) 086 (058-129)
073 (012-447)
140 (045-440) 100 (050-200) 105 (069-160)
143 (072-283)
08
0 0 07
5
026 (006-123)
Summary bull Among patients with an ACS with or without ST-segment
elevation who underwent invasive management the use
of radial access for coronary angiography plusmn PCI reduced
the rate of net adverse clinical events with a number
needed to treat for benefit of 53
ndash Differences between groups were driven by reductions in BARC
major bleeding unrelated to CABG and all-cause mortality with
radial access
bull Our results in conjunction with the updated meta-
analysis suggest that radial approach should
become the default access for patients with
ACS undergoing invasive management
Radial Acces 61000 menos Muertes
LA VIA TRANSRADIAL DEBERIA SER EL ACCESO DE ELECCION o ldquo DEFAULTrdquo PARA LOS PACIENTES CON SCA TRATADOS CON INTERVENCIONISMO PERCUTANEO
LA VIA TRANSRADIAL DEBERIA SER EL ACCESO DE ELECCION PARA TODO PACIENTE CONSIN SCA TRATADOS CON INTERVENCIONISMO PERCUTANEO
GRACIAS POR SU ATENCION
MACE
Mortality
No interaction between access and anticoagulant use in a post- hoc analysis of the subgroup of 7213 patients randomized to bivalirudin or unfractionated heparin for the two co-primary outcomes all-cause mortality or BARC 3 or 5 bleeding
Relevance of bleeding as a clinical endpoint
bull Availability of potent antithrombotic therapy including ndash ASA ndash P2Y12 inhibitors (clopidogrel prasugrel ticagrelor) ndash heparin ndash GP IIbIIIa inhibitors ndash direct thrombin inhibitors
bull has led to a reduction in ischemic events bull but is associated with an increased risk of
bleeding bull the increase in bleeding is associated with worse
clinical outcome
Rationale for a new bleeding definition
bull Increased importance of bleeding as prognostic factor
bull Need for assessment of bleeding in RCTs and registries
bull Lack of comparability bull Need for standardized definitions to avoid
erroneous conclusions
ndash regarding safety of a given agent ndash regarding superiority of one agent over another
Open questions regarding BARC
bull Why 48-hour window for CABG-related bleeding
bull Why type 1 bdquonot actionableldquo when patient may bdquotake actionldquo such as discontinuing medication (with potentially serious consequences such as ST)
bull Why consider intraocular bleed equivalent to intracranial bleed for BARC 3c
bull Type 1 bleed subject to misinterpretation by the patient
Hicks et al (editorial) Circulation 20111232664
Conclusion
bull BARC is a new objective hierarchically graded classification of bleeding
(Mehran Circulation [June 14] 20111232736)
bull BARC is based on consensus rather than data-driven
bull Prospective validation is warranted ndash across the spectrum of IHD
ndash across management strategies (conservative invasive)
ndash in the context of all invasive procedures (PCI CABG endovascular TAVI)
Conclusion (2)
bull Final validation of BARC and proof of its utility depend on
ndash its use by all future RCTs as common safety endpoint
ndash unanimous assessment procedure (questionnaires)
bull More important than using one or the other bleeding risk score is the agreement and commitment among clinical trialists to use the same score for comparability of data
Am Heart J 2009 Jan157(1)164-9 Epub 2008 Nov 6
Hypothetical mechanisms linking bleeding and mortality
Steg P G et al Eur Heart J 2011321854-
1864
Existing bleeding scores
bull TIMI Laboratory-based (hemoglobin hematocrit decrease)
bull GUSTO Clinical (severity)-based
bull GRACE Simplified laboratory and clinical
bull CURE Major minor (combined clin + lab)
bull ACUITY Major (intracranial-ocular access-site retroperit) lab
bull REPLACE-2 bull ISAR-REACT 3 bull PLATO bull STEEPLE bull CURRENT-OASIS
Thrombolysis conservative
PCI-based
BARC (Bleeding Academic Research Consortium) definitions
Mehran et al Circulation 20111232736-2747
bull Type 0 no evidence of bleeding bull Type 1 bleeding that is not actionable without
need for hospitalization or treatment (eg bruising hematoma nosebleeds etc)
bull Type 2 any clinically overt sign of hemorrhage that is actionable but does not meet criteria for type 3 4 or 5 Must meet at least 1 of following criteria ndash Requires intervention ndash Leads to hospitalization MANEJO MEDICO ndash Prompts evaluation
BARC (Bleeding Academic Research Consortium) definitions
Mehran et al Circulation 20111232736-2747
bull Type 3 clinical laboratory andor imaging evidence of bleeding with healthcare provider responses ndash BARC type 3a
bull any transfusion with overt bleeding bull overt bleeding plus hemoglobin drop ge3 to lt5 gdL
ndash BARC type 3b bull overt bleeding plus hemoglobin drop gt5 gdL bull Cardiac tamponade bull Bleeding requiring surgical intervention for control (excluding dentalnasalskinhemorrhoid) bull Bleeding requiring intravenous vasoactive drugs
ndash BARC type 3c bull Intracranial hemorrhage subcategories confirmed by autopsy
imaging or lumbar puncture bull Intraocular bleed compromising vision
BARC Bleeding Academic Research Consortium) definitions
Mehran et al Circulation 20111232736-2747
bull Type 4 Coronary Artery Bypass Graftndashrelated bleeding ndash Perioperative intracranial bleeding within 48 hours ndash Reoperation after closure of sternotomy for the purpose of controlling bleeding ndash Transfusion of ge5 U whole blood or packed red blood cells within a 48-hour period ndash Chest tube output 2 L within a 24-hour period
bull Type 5 ndash fatal bleeding bull Probable fatal bleeding (type 5a)
ndash bleeding that is clinically suspicious as the cause of death but the bleeding is not directly observed and there is no autopsy or confirmatory imaging
bull Definite fatal bleeding (type 5b) ndash bleeding that is directly observed (by either clinical specimen [blood
emesis stool etc] or imaging) or confirmed on autopsy
26 VCD
11
NSTEACS or STEMI with invasive management Aspirin+P2Y12 blocker
Trans-Femoral Access
Trans-Radial Access
To demonstrate that trans-radial intervention as
compared to femoral access site is associated to lower
rate of the composite endpoint of Death MI or Stroke
within the first 30 days
1deg co-Primary Objective
6 vs 42 βlt10 α 25 8200 patients
Adaptive study Design sample size (SS) will be increased
by the cross-over rate at 70 of planned SS
MATRIX Access site NCT01433627
MATRIX Access
39 93 132 200 276 380 490 685 857 1002 1190
1400 1684 1972 2248
2584 2926
3256 3560
3875 4144
4452 4726
5000 5322
5655 5896 6184
6458 6742 6982 7235 7444 7638 7844 8073
8404
Cumulative enrollment by month
8404
8404
8404 patients with ACS undergoing coronary angiography plusmn PCI from 11th Oct 2011 to 7th Nov 2014
Operator Eligibility Criteria Interventional cardiologist expertise in TRI and TFI including at least 75 transradial coronary interventions and at least 50 of interventions performed via radial route in the year preceding site initiation
Complete follow-up to 30 days available in 4183 (997) of radial and 4191 (99middot6) of femoral cohorts
Am Heart J 2014 Dec168(6)838-45e6
Cross Over and Procedural Success Rates
941 of radial and 974 of femoral cohorts received respective treatment as allocated
In 58 of radial and 23 of TF cohort the allocated access was attempted but failed
In 3 (01) in the radial and 13 (03) patients in the femoral groups the allocated access was not attempted
P=077 Plt0001
TIMI lt3 andor final stenosis gt30
88
103
15 significant reduction at nominal 5 alpha
which is however NOT significant at the pre-specificed
alpha of 25
Primary EP MACE
Femoral
Radial
Rate Ratio 083 95 CI 073 to 096 p=00092
117
98
NNTB 53 Femoral
Radial
Primary EP NACE
Mortalidad Total
IAM
Fatal and ST EPs All-Cause Cardiac non-CV mortality type of stent thrombosis
RR072
(053-099)
P=0045
RR 075
(054-104)
P=008 1
13
06
1
0
02
04
06
08
1
12
14
Radial Femoral
P=069
P=066
Mortality Stent Thrombosis
NNTB 167
Bleeding endpoints BARC TIMI GUSTO access vs non-access related
14
25
P=0013
RR 067 049-092
P=00004
RR 037 021-066
BARC 3 or 5
P=00098
RR 064 045-090
P=008
RR 072 050-104 P=020
RR 078 053-114
Major
or minor
moderate
or severe
P=082
P=068
Rardial Better Femoral Better 1
HAZARD RATIO (95 CI)
P-VALUES
Superiority Interaction
089 Intermediate (548-991)
075 (060-094)
104 (082-132) 076 0011
Centrersquos annual
volume of PCI
Low (247-544)
Intermediate (654-790)
Centrersquos
Proportion of
radial PCI
Low (149-644)
NSTE-ACS (tpndash) ACS type
STEMI
lt75 Age
ge75 023 088 (070-109)
082 (068-097) 0023 062
NACE Subgroup Analysis
High (1000-1950)
High (800-980)
NSTE-ACS (tp+)
Men Sex
Women
lt25 BMI
ge25
No
Ticagrelor or
prasugrel Yes
No Diabetes
Yes
lt60 GFR
ge60
No
History of
PVD Yes
2 025 050
075 (058-097) 0025
00048
101 (079-129)
095 (075 -122) 071
095
064 (051-080) lt0001
044
086 (068-108)
058 (033-103) 0059
019
085 (071-102) 007
0012 072 (056-093)
089 (076-105) 016 018
009 086 (073-102)
079 (063-099) 0038 053
007 083 (068-102)
084 (070-101) 006 094
045 091 (071-117)
080 (068-094) 008 043
001 078 (065-094)
086 (070-107) 018 051
060 091 (064-130)
083 (071-096) 0012 064
Radial Better Femoral Better 1
HAZARD RATIO (95 CI)
P-VALUES
Superiority Interaction
Intermediate (654-790)
Centrersquos
Proportion
of radial PCI
Low (149-644)
NSTE-ACS (tpndash) ACS
type
STEMI
Subgroup Analysis
High (800-980)
NSTE-ACS (tp+)
2
00157
128 (071-232)
069 (040 -119) 018
041
048 (028-081) 0006
010
087 (059-129) 049
049 (028-087) 0012
Intermediate (654-790) Centrersquos
Proportion
of radial PCI
Low (149-644)
NSTE-ACS (tpndash) ACS
type
STEMI
High (800-980)
NSTE-ACS (tp+)
020
090 (054-150)
057 (031 -103) 006
068
056 (032-097) 0035
054
062 (041-094)
166 (028-100) 058
0022
070 (042-117) 017
Mortality
Bleeding
4 050 025
1 2 050 025
Updated Meta-analysis 19328 ACS patients being randomly allocated to radial or femoral access
Rardial Better Femoral Better 1 4 025 050 2
Pre-Rival RIVAL Post-RIVAL MATRI
X Combined
Non-CABG
major bleeds
Death
myocardial
infarction or
stroke
Death
Myocardial
Infarction
Stroke
Pre-Rival RIVAL Post-RIVAL MATRI
X Combined
Pre-Rival RIVAL Post-RIVAL MATRI
X Combined
Pre-Rival RIVAL Post-RIVAL MATRI
X Combined
Pre-Rival RIVAL Post-RIVAL MATRI
X Combined
SUBGROUP Risk Ratio (95CI) P Value
Heterogenity
P Value I2
073 (043-123) 039 (023-067)
058 (046-072)
041 (022-076)
lt00001 0 05
1
067 (048-093) 086 (076-098) 086 (077-095)
098 (076-127)
00051 0 09
7
058 (039-087) 073 (053-099) 072 (060-088) 00011 0 10
0
085 (039-190) 091 (078-106) 091 (079-104)
092 (065-131)
01
6 0 08
8
068 (049-092)
082 (052-129)
077 (046-128) 086 (058-129)
073 (012-447)
140 (045-440) 100 (050-200) 105 (069-160)
143 (072-283)
08
0 0 07
5
026 (006-123)
Summary bull Among patients with an ACS with or without ST-segment
elevation who underwent invasive management the use
of radial access for coronary angiography plusmn PCI reduced
the rate of net adverse clinical events with a number
needed to treat for benefit of 53
ndash Differences between groups were driven by reductions in BARC
major bleeding unrelated to CABG and all-cause mortality with
radial access
bull Our results in conjunction with the updated meta-
analysis suggest that radial approach should
become the default access for patients with
ACS undergoing invasive management
Radial Acces 61000 menos Muertes
LA VIA TRANSRADIAL DEBERIA SER EL ACCESO DE ELECCION o ldquo DEFAULTrdquo PARA LOS PACIENTES CON SCA TRATADOS CON INTERVENCIONISMO PERCUTANEO
LA VIA TRANSRADIAL DEBERIA SER EL ACCESO DE ELECCION PARA TODO PACIENTE CONSIN SCA TRATADOS CON INTERVENCIONISMO PERCUTANEO
GRACIAS POR SU ATENCION
MACE
Mortality
No interaction between access and anticoagulant use in a post- hoc analysis of the subgroup of 7213 patients randomized to bivalirudin or unfractionated heparin for the two co-primary outcomes all-cause mortality or BARC 3 or 5 bleeding
Relevance of bleeding as a clinical endpoint
bull Availability of potent antithrombotic therapy including ndash ASA ndash P2Y12 inhibitors (clopidogrel prasugrel ticagrelor) ndash heparin ndash GP IIbIIIa inhibitors ndash direct thrombin inhibitors
bull has led to a reduction in ischemic events bull but is associated with an increased risk of
bleeding bull the increase in bleeding is associated with worse
clinical outcome
Rationale for a new bleeding definition
bull Increased importance of bleeding as prognostic factor
bull Need for assessment of bleeding in RCTs and registries
bull Lack of comparability bull Need for standardized definitions to avoid
erroneous conclusions
ndash regarding safety of a given agent ndash regarding superiority of one agent over another
Open questions regarding BARC
bull Why 48-hour window for CABG-related bleeding
bull Why type 1 bdquonot actionableldquo when patient may bdquotake actionldquo such as discontinuing medication (with potentially serious consequences such as ST)
bull Why consider intraocular bleed equivalent to intracranial bleed for BARC 3c
bull Type 1 bleed subject to misinterpretation by the patient
Hicks et al (editorial) Circulation 20111232664
Conclusion
bull BARC is a new objective hierarchically graded classification of bleeding
(Mehran Circulation [June 14] 20111232736)
bull BARC is based on consensus rather than data-driven
bull Prospective validation is warranted ndash across the spectrum of IHD
ndash across management strategies (conservative invasive)
ndash in the context of all invasive procedures (PCI CABG endovascular TAVI)
Conclusion (2)
bull Final validation of BARC and proof of its utility depend on
ndash its use by all future RCTs as common safety endpoint
ndash unanimous assessment procedure (questionnaires)
bull More important than using one or the other bleeding risk score is the agreement and commitment among clinical trialists to use the same score for comparability of data
Hypothetical mechanisms linking bleeding and mortality
Steg P G et al Eur Heart J 2011321854-
1864
Existing bleeding scores
bull TIMI Laboratory-based (hemoglobin hematocrit decrease)
bull GUSTO Clinical (severity)-based
bull GRACE Simplified laboratory and clinical
bull CURE Major minor (combined clin + lab)
bull ACUITY Major (intracranial-ocular access-site retroperit) lab
bull REPLACE-2 bull ISAR-REACT 3 bull PLATO bull STEEPLE bull CURRENT-OASIS
Thrombolysis conservative
PCI-based
BARC (Bleeding Academic Research Consortium) definitions
Mehran et al Circulation 20111232736-2747
bull Type 0 no evidence of bleeding bull Type 1 bleeding that is not actionable without
need for hospitalization or treatment (eg bruising hematoma nosebleeds etc)
bull Type 2 any clinically overt sign of hemorrhage that is actionable but does not meet criteria for type 3 4 or 5 Must meet at least 1 of following criteria ndash Requires intervention ndash Leads to hospitalization MANEJO MEDICO ndash Prompts evaluation
BARC (Bleeding Academic Research Consortium) definitions
Mehran et al Circulation 20111232736-2747
bull Type 3 clinical laboratory andor imaging evidence of bleeding with healthcare provider responses ndash BARC type 3a
bull any transfusion with overt bleeding bull overt bleeding plus hemoglobin drop ge3 to lt5 gdL
ndash BARC type 3b bull overt bleeding plus hemoglobin drop gt5 gdL bull Cardiac tamponade bull Bleeding requiring surgical intervention for control (excluding dentalnasalskinhemorrhoid) bull Bleeding requiring intravenous vasoactive drugs
ndash BARC type 3c bull Intracranial hemorrhage subcategories confirmed by autopsy
imaging or lumbar puncture bull Intraocular bleed compromising vision
BARC Bleeding Academic Research Consortium) definitions
Mehran et al Circulation 20111232736-2747
bull Type 4 Coronary Artery Bypass Graftndashrelated bleeding ndash Perioperative intracranial bleeding within 48 hours ndash Reoperation after closure of sternotomy for the purpose of controlling bleeding ndash Transfusion of ge5 U whole blood or packed red blood cells within a 48-hour period ndash Chest tube output 2 L within a 24-hour period
bull Type 5 ndash fatal bleeding bull Probable fatal bleeding (type 5a)
ndash bleeding that is clinically suspicious as the cause of death but the bleeding is not directly observed and there is no autopsy or confirmatory imaging
bull Definite fatal bleeding (type 5b) ndash bleeding that is directly observed (by either clinical specimen [blood
emesis stool etc] or imaging) or confirmed on autopsy
26 VCD
11
NSTEACS or STEMI with invasive management Aspirin+P2Y12 blocker
Trans-Femoral Access
Trans-Radial Access
To demonstrate that trans-radial intervention as
compared to femoral access site is associated to lower
rate of the composite endpoint of Death MI or Stroke
within the first 30 days
1deg co-Primary Objective
6 vs 42 βlt10 α 25 8200 patients
Adaptive study Design sample size (SS) will be increased
by the cross-over rate at 70 of planned SS
MATRIX Access site NCT01433627
MATRIX Access
39 93 132 200 276 380 490 685 857 1002 1190
1400 1684 1972 2248
2584 2926
3256 3560
3875 4144
4452 4726
5000 5322
5655 5896 6184
6458 6742 6982 7235 7444 7638 7844 8073
8404
Cumulative enrollment by month
8404
8404
8404 patients with ACS undergoing coronary angiography plusmn PCI from 11th Oct 2011 to 7th Nov 2014
Operator Eligibility Criteria Interventional cardiologist expertise in TRI and TFI including at least 75 transradial coronary interventions and at least 50 of interventions performed via radial route in the year preceding site initiation
Complete follow-up to 30 days available in 4183 (997) of radial and 4191 (99middot6) of femoral cohorts
Am Heart J 2014 Dec168(6)838-45e6
Cross Over and Procedural Success Rates
941 of radial and 974 of femoral cohorts received respective treatment as allocated
In 58 of radial and 23 of TF cohort the allocated access was attempted but failed
In 3 (01) in the radial and 13 (03) patients in the femoral groups the allocated access was not attempted
P=077 Plt0001
TIMI lt3 andor final stenosis gt30
88
103
15 significant reduction at nominal 5 alpha
which is however NOT significant at the pre-specificed
alpha of 25
Primary EP MACE
Femoral
Radial
Rate Ratio 083 95 CI 073 to 096 p=00092
117
98
NNTB 53 Femoral
Radial
Primary EP NACE
Mortalidad Total
IAM
Fatal and ST EPs All-Cause Cardiac non-CV mortality type of stent thrombosis
RR072
(053-099)
P=0045
RR 075
(054-104)
P=008 1
13
06
1
0
02
04
06
08
1
12
14
Radial Femoral
P=069
P=066
Mortality Stent Thrombosis
NNTB 167
Bleeding endpoints BARC TIMI GUSTO access vs non-access related
14
25
P=0013
RR 067 049-092
P=00004
RR 037 021-066
BARC 3 or 5
P=00098
RR 064 045-090
P=008
RR 072 050-104 P=020
RR 078 053-114
Major
or minor
moderate
or severe
P=082
P=068
Rardial Better Femoral Better 1
HAZARD RATIO (95 CI)
P-VALUES
Superiority Interaction
089 Intermediate (548-991)
075 (060-094)
104 (082-132) 076 0011
Centrersquos annual
volume of PCI
Low (247-544)
Intermediate (654-790)
Centrersquos
Proportion of
radial PCI
Low (149-644)
NSTE-ACS (tpndash) ACS type
STEMI
lt75 Age
ge75 023 088 (070-109)
082 (068-097) 0023 062
NACE Subgroup Analysis
High (1000-1950)
High (800-980)
NSTE-ACS (tp+)
Men Sex
Women
lt25 BMI
ge25
No
Ticagrelor or
prasugrel Yes
No Diabetes
Yes
lt60 GFR
ge60
No
History of
PVD Yes
2 025 050
075 (058-097) 0025
00048
101 (079-129)
095 (075 -122) 071
095
064 (051-080) lt0001
044
086 (068-108)
058 (033-103) 0059
019
085 (071-102) 007
0012 072 (056-093)
089 (076-105) 016 018
009 086 (073-102)
079 (063-099) 0038 053
007 083 (068-102)
084 (070-101) 006 094
045 091 (071-117)
080 (068-094) 008 043
001 078 (065-094)
086 (070-107) 018 051
060 091 (064-130)
083 (071-096) 0012 064
Radial Better Femoral Better 1
HAZARD RATIO (95 CI)
P-VALUES
Superiority Interaction
Intermediate (654-790)
Centrersquos
Proportion
of radial PCI
Low (149-644)
NSTE-ACS (tpndash) ACS
type
STEMI
Subgroup Analysis
High (800-980)
NSTE-ACS (tp+)
2
00157
128 (071-232)
069 (040 -119) 018
041
048 (028-081) 0006
010
087 (059-129) 049
049 (028-087) 0012
Intermediate (654-790) Centrersquos
Proportion
of radial PCI
Low (149-644)
NSTE-ACS (tpndash) ACS
type
STEMI
High (800-980)
NSTE-ACS (tp+)
020
090 (054-150)
057 (031 -103) 006
068
056 (032-097) 0035
054
062 (041-094)
166 (028-100) 058
0022
070 (042-117) 017
Mortality
Bleeding
4 050 025
1 2 050 025
Updated Meta-analysis 19328 ACS patients being randomly allocated to radial or femoral access
Rardial Better Femoral Better 1 4 025 050 2
Pre-Rival RIVAL Post-RIVAL MATRI
X Combined
Non-CABG
major bleeds
Death
myocardial
infarction or
stroke
Death
Myocardial
Infarction
Stroke
Pre-Rival RIVAL Post-RIVAL MATRI
X Combined
Pre-Rival RIVAL Post-RIVAL MATRI
X Combined
Pre-Rival RIVAL Post-RIVAL MATRI
X Combined
Pre-Rival RIVAL Post-RIVAL MATRI
X Combined
SUBGROUP Risk Ratio (95CI) P Value
Heterogenity
P Value I2
073 (043-123) 039 (023-067)
058 (046-072)
041 (022-076)
lt00001 0 05
1
067 (048-093) 086 (076-098) 086 (077-095)
098 (076-127)
00051 0 09
7
058 (039-087) 073 (053-099) 072 (060-088) 00011 0 10
0
085 (039-190) 091 (078-106) 091 (079-104)
092 (065-131)
01
6 0 08
8
068 (049-092)
082 (052-129)
077 (046-128) 086 (058-129)
073 (012-447)
140 (045-440) 100 (050-200) 105 (069-160)
143 (072-283)
08
0 0 07
5
026 (006-123)
Summary bull Among patients with an ACS with or without ST-segment
elevation who underwent invasive management the use
of radial access for coronary angiography plusmn PCI reduced
the rate of net adverse clinical events with a number
needed to treat for benefit of 53
ndash Differences between groups were driven by reductions in BARC
major bleeding unrelated to CABG and all-cause mortality with
radial access
bull Our results in conjunction with the updated meta-
analysis suggest that radial approach should
become the default access for patients with
ACS undergoing invasive management
Radial Acces 61000 menos Muertes
LA VIA TRANSRADIAL DEBERIA SER EL ACCESO DE ELECCION o ldquo DEFAULTrdquo PARA LOS PACIENTES CON SCA TRATADOS CON INTERVENCIONISMO PERCUTANEO
LA VIA TRANSRADIAL DEBERIA SER EL ACCESO DE ELECCION PARA TODO PACIENTE CONSIN SCA TRATADOS CON INTERVENCIONISMO PERCUTANEO
GRACIAS POR SU ATENCION
MACE
Mortality
No interaction between access and anticoagulant use in a post- hoc analysis of the subgroup of 7213 patients randomized to bivalirudin or unfractionated heparin for the two co-primary outcomes all-cause mortality or BARC 3 or 5 bleeding
Relevance of bleeding as a clinical endpoint
bull Availability of potent antithrombotic therapy including ndash ASA ndash P2Y12 inhibitors (clopidogrel prasugrel ticagrelor) ndash heparin ndash GP IIbIIIa inhibitors ndash direct thrombin inhibitors
bull has led to a reduction in ischemic events bull but is associated with an increased risk of
bleeding bull the increase in bleeding is associated with worse
clinical outcome
Rationale for a new bleeding definition
bull Increased importance of bleeding as prognostic factor
bull Need for assessment of bleeding in RCTs and registries
bull Lack of comparability bull Need for standardized definitions to avoid
erroneous conclusions
ndash regarding safety of a given agent ndash regarding superiority of one agent over another
Open questions regarding BARC
bull Why 48-hour window for CABG-related bleeding
bull Why type 1 bdquonot actionableldquo when patient may bdquotake actionldquo such as discontinuing medication (with potentially serious consequences such as ST)
bull Why consider intraocular bleed equivalent to intracranial bleed for BARC 3c
bull Type 1 bleed subject to misinterpretation by the patient
Hicks et al (editorial) Circulation 20111232664
Conclusion
bull BARC is a new objective hierarchically graded classification of bleeding
(Mehran Circulation [June 14] 20111232736)
bull BARC is based on consensus rather than data-driven
bull Prospective validation is warranted ndash across the spectrum of IHD
ndash across management strategies (conservative invasive)
ndash in the context of all invasive procedures (PCI CABG endovascular TAVI)
Conclusion (2)
bull Final validation of BARC and proof of its utility depend on
ndash its use by all future RCTs as common safety endpoint
ndash unanimous assessment procedure (questionnaires)
bull More important than using one or the other bleeding risk score is the agreement and commitment among clinical trialists to use the same score for comparability of data
Existing bleeding scores
bull TIMI Laboratory-based (hemoglobin hematocrit decrease)
bull GUSTO Clinical (severity)-based
bull GRACE Simplified laboratory and clinical
bull CURE Major minor (combined clin + lab)
bull ACUITY Major (intracranial-ocular access-site retroperit) lab
bull REPLACE-2 bull ISAR-REACT 3 bull PLATO bull STEEPLE bull CURRENT-OASIS
Thrombolysis conservative
PCI-based
BARC (Bleeding Academic Research Consortium) definitions
Mehran et al Circulation 20111232736-2747
bull Type 0 no evidence of bleeding bull Type 1 bleeding that is not actionable without
need for hospitalization or treatment (eg bruising hematoma nosebleeds etc)
bull Type 2 any clinically overt sign of hemorrhage that is actionable but does not meet criteria for type 3 4 or 5 Must meet at least 1 of following criteria ndash Requires intervention ndash Leads to hospitalization MANEJO MEDICO ndash Prompts evaluation
BARC (Bleeding Academic Research Consortium) definitions
Mehran et al Circulation 20111232736-2747
bull Type 3 clinical laboratory andor imaging evidence of bleeding with healthcare provider responses ndash BARC type 3a
bull any transfusion with overt bleeding bull overt bleeding plus hemoglobin drop ge3 to lt5 gdL
ndash BARC type 3b bull overt bleeding plus hemoglobin drop gt5 gdL bull Cardiac tamponade bull Bleeding requiring surgical intervention for control (excluding dentalnasalskinhemorrhoid) bull Bleeding requiring intravenous vasoactive drugs
ndash BARC type 3c bull Intracranial hemorrhage subcategories confirmed by autopsy
imaging or lumbar puncture bull Intraocular bleed compromising vision
BARC Bleeding Academic Research Consortium) definitions
Mehran et al Circulation 20111232736-2747
bull Type 4 Coronary Artery Bypass Graftndashrelated bleeding ndash Perioperative intracranial bleeding within 48 hours ndash Reoperation after closure of sternotomy for the purpose of controlling bleeding ndash Transfusion of ge5 U whole blood or packed red blood cells within a 48-hour period ndash Chest tube output 2 L within a 24-hour period
bull Type 5 ndash fatal bleeding bull Probable fatal bleeding (type 5a)
ndash bleeding that is clinically suspicious as the cause of death but the bleeding is not directly observed and there is no autopsy or confirmatory imaging
bull Definite fatal bleeding (type 5b) ndash bleeding that is directly observed (by either clinical specimen [blood
emesis stool etc] or imaging) or confirmed on autopsy
26 VCD
11
NSTEACS or STEMI with invasive management Aspirin+P2Y12 blocker
Trans-Femoral Access
Trans-Radial Access
To demonstrate that trans-radial intervention as
compared to femoral access site is associated to lower
rate of the composite endpoint of Death MI or Stroke
within the first 30 days
1deg co-Primary Objective
6 vs 42 βlt10 α 25 8200 patients
Adaptive study Design sample size (SS) will be increased
by the cross-over rate at 70 of planned SS
MATRIX Access site NCT01433627
MATRIX Access
39 93 132 200 276 380 490 685 857 1002 1190
1400 1684 1972 2248
2584 2926
3256 3560
3875 4144
4452 4726
5000 5322
5655 5896 6184
6458 6742 6982 7235 7444 7638 7844 8073
8404
Cumulative enrollment by month
8404
8404
8404 patients with ACS undergoing coronary angiography plusmn PCI from 11th Oct 2011 to 7th Nov 2014
Operator Eligibility Criteria Interventional cardiologist expertise in TRI and TFI including at least 75 transradial coronary interventions and at least 50 of interventions performed via radial route in the year preceding site initiation
Complete follow-up to 30 days available in 4183 (997) of radial and 4191 (99middot6) of femoral cohorts
Am Heart J 2014 Dec168(6)838-45e6
Cross Over and Procedural Success Rates
941 of radial and 974 of femoral cohorts received respective treatment as allocated
In 58 of radial and 23 of TF cohort the allocated access was attempted but failed
In 3 (01) in the radial and 13 (03) patients in the femoral groups the allocated access was not attempted
P=077 Plt0001
TIMI lt3 andor final stenosis gt30
88
103
15 significant reduction at nominal 5 alpha
which is however NOT significant at the pre-specificed
alpha of 25
Primary EP MACE
Femoral
Radial
Rate Ratio 083 95 CI 073 to 096 p=00092
117
98
NNTB 53 Femoral
Radial
Primary EP NACE
Mortalidad Total
IAM
Fatal and ST EPs All-Cause Cardiac non-CV mortality type of stent thrombosis
RR072
(053-099)
P=0045
RR 075
(054-104)
P=008 1
13
06
1
0
02
04
06
08
1
12
14
Radial Femoral
P=069
P=066
Mortality Stent Thrombosis
NNTB 167
Bleeding endpoints BARC TIMI GUSTO access vs non-access related
14
25
P=0013
RR 067 049-092
P=00004
RR 037 021-066
BARC 3 or 5
P=00098
RR 064 045-090
P=008
RR 072 050-104 P=020
RR 078 053-114
Major
or minor
moderate
or severe
P=082
P=068
Rardial Better Femoral Better 1
HAZARD RATIO (95 CI)
P-VALUES
Superiority Interaction
089 Intermediate (548-991)
075 (060-094)
104 (082-132) 076 0011
Centrersquos annual
volume of PCI
Low (247-544)
Intermediate (654-790)
Centrersquos
Proportion of
radial PCI
Low (149-644)
NSTE-ACS (tpndash) ACS type
STEMI
lt75 Age
ge75 023 088 (070-109)
082 (068-097) 0023 062
NACE Subgroup Analysis
High (1000-1950)
High (800-980)
NSTE-ACS (tp+)
Men Sex
Women
lt25 BMI
ge25
No
Ticagrelor or
prasugrel Yes
No Diabetes
Yes
lt60 GFR
ge60
No
History of
PVD Yes
2 025 050
075 (058-097) 0025
00048
101 (079-129)
095 (075 -122) 071
095
064 (051-080) lt0001
044
086 (068-108)
058 (033-103) 0059
019
085 (071-102) 007
0012 072 (056-093)
089 (076-105) 016 018
009 086 (073-102)
079 (063-099) 0038 053
007 083 (068-102)
084 (070-101) 006 094
045 091 (071-117)
080 (068-094) 008 043
001 078 (065-094)
086 (070-107) 018 051
060 091 (064-130)
083 (071-096) 0012 064
Radial Better Femoral Better 1
HAZARD RATIO (95 CI)
P-VALUES
Superiority Interaction
Intermediate (654-790)
Centrersquos
Proportion
of radial PCI
Low (149-644)
NSTE-ACS (tpndash) ACS
type
STEMI
Subgroup Analysis
High (800-980)
NSTE-ACS (tp+)
2
00157
128 (071-232)
069 (040 -119) 018
041
048 (028-081) 0006
010
087 (059-129) 049
049 (028-087) 0012
Intermediate (654-790) Centrersquos
Proportion
of radial PCI
Low (149-644)
NSTE-ACS (tpndash) ACS
type
STEMI
High (800-980)
NSTE-ACS (tp+)
020
090 (054-150)
057 (031 -103) 006
068
056 (032-097) 0035
054
062 (041-094)
166 (028-100) 058
0022
070 (042-117) 017
Mortality
Bleeding
4 050 025
1 2 050 025
Updated Meta-analysis 19328 ACS patients being randomly allocated to radial or femoral access
Rardial Better Femoral Better 1 4 025 050 2
Pre-Rival RIVAL Post-RIVAL MATRI
X Combined
Non-CABG
major bleeds
Death
myocardial
infarction or
stroke
Death
Myocardial
Infarction
Stroke
Pre-Rival RIVAL Post-RIVAL MATRI
X Combined
Pre-Rival RIVAL Post-RIVAL MATRI
X Combined
Pre-Rival RIVAL Post-RIVAL MATRI
X Combined
Pre-Rival RIVAL Post-RIVAL MATRI
X Combined
SUBGROUP Risk Ratio (95CI) P Value
Heterogenity
P Value I2
073 (043-123) 039 (023-067)
058 (046-072)
041 (022-076)
lt00001 0 05
1
067 (048-093) 086 (076-098) 086 (077-095)
098 (076-127)
00051 0 09
7
058 (039-087) 073 (053-099) 072 (060-088) 00011 0 10
0
085 (039-190) 091 (078-106) 091 (079-104)
092 (065-131)
01
6 0 08
8
068 (049-092)
082 (052-129)
077 (046-128) 086 (058-129)
073 (012-447)
140 (045-440) 100 (050-200) 105 (069-160)
143 (072-283)
08
0 0 07
5
026 (006-123)
Summary bull Among patients with an ACS with or without ST-segment
elevation who underwent invasive management the use
of radial access for coronary angiography plusmn PCI reduced
the rate of net adverse clinical events with a number
needed to treat for benefit of 53
ndash Differences between groups were driven by reductions in BARC
major bleeding unrelated to CABG and all-cause mortality with
radial access
bull Our results in conjunction with the updated meta-
analysis suggest that radial approach should
become the default access for patients with
ACS undergoing invasive management
Radial Acces 61000 menos Muertes
LA VIA TRANSRADIAL DEBERIA SER EL ACCESO DE ELECCION o ldquo DEFAULTrdquo PARA LOS PACIENTES CON SCA TRATADOS CON INTERVENCIONISMO PERCUTANEO
LA VIA TRANSRADIAL DEBERIA SER EL ACCESO DE ELECCION PARA TODO PACIENTE CONSIN SCA TRATADOS CON INTERVENCIONISMO PERCUTANEO
GRACIAS POR SU ATENCION
MACE
Mortality
No interaction between access and anticoagulant use in a post- hoc analysis of the subgroup of 7213 patients randomized to bivalirudin or unfractionated heparin for the two co-primary outcomes all-cause mortality or BARC 3 or 5 bleeding
Relevance of bleeding as a clinical endpoint
bull Availability of potent antithrombotic therapy including ndash ASA ndash P2Y12 inhibitors (clopidogrel prasugrel ticagrelor) ndash heparin ndash GP IIbIIIa inhibitors ndash direct thrombin inhibitors
bull has led to a reduction in ischemic events bull but is associated with an increased risk of
bleeding bull the increase in bleeding is associated with worse
clinical outcome
Rationale for a new bleeding definition
bull Increased importance of bleeding as prognostic factor
bull Need for assessment of bleeding in RCTs and registries
bull Lack of comparability bull Need for standardized definitions to avoid
erroneous conclusions
ndash regarding safety of a given agent ndash regarding superiority of one agent over another
Open questions regarding BARC
bull Why 48-hour window for CABG-related bleeding
bull Why type 1 bdquonot actionableldquo when patient may bdquotake actionldquo such as discontinuing medication (with potentially serious consequences such as ST)
bull Why consider intraocular bleed equivalent to intracranial bleed for BARC 3c
bull Type 1 bleed subject to misinterpretation by the patient
Hicks et al (editorial) Circulation 20111232664
Conclusion
bull BARC is a new objective hierarchically graded classification of bleeding
(Mehran Circulation [June 14] 20111232736)
bull BARC is based on consensus rather than data-driven
bull Prospective validation is warranted ndash across the spectrum of IHD
ndash across management strategies (conservative invasive)
ndash in the context of all invasive procedures (PCI CABG endovascular TAVI)
Conclusion (2)
bull Final validation of BARC and proof of its utility depend on
ndash its use by all future RCTs as common safety endpoint
ndash unanimous assessment procedure (questionnaires)
bull More important than using one or the other bleeding risk score is the agreement and commitment among clinical trialists to use the same score for comparability of data
BARC (Bleeding Academic Research Consortium) definitions
Mehran et al Circulation 20111232736-2747
bull Type 0 no evidence of bleeding bull Type 1 bleeding that is not actionable without
need for hospitalization or treatment (eg bruising hematoma nosebleeds etc)
bull Type 2 any clinically overt sign of hemorrhage that is actionable but does not meet criteria for type 3 4 or 5 Must meet at least 1 of following criteria ndash Requires intervention ndash Leads to hospitalization MANEJO MEDICO ndash Prompts evaluation
BARC (Bleeding Academic Research Consortium) definitions
Mehran et al Circulation 20111232736-2747
bull Type 3 clinical laboratory andor imaging evidence of bleeding with healthcare provider responses ndash BARC type 3a
bull any transfusion with overt bleeding bull overt bleeding plus hemoglobin drop ge3 to lt5 gdL
ndash BARC type 3b bull overt bleeding plus hemoglobin drop gt5 gdL bull Cardiac tamponade bull Bleeding requiring surgical intervention for control (excluding dentalnasalskinhemorrhoid) bull Bleeding requiring intravenous vasoactive drugs
ndash BARC type 3c bull Intracranial hemorrhage subcategories confirmed by autopsy
imaging or lumbar puncture bull Intraocular bleed compromising vision
BARC Bleeding Academic Research Consortium) definitions
Mehran et al Circulation 20111232736-2747
bull Type 4 Coronary Artery Bypass Graftndashrelated bleeding ndash Perioperative intracranial bleeding within 48 hours ndash Reoperation after closure of sternotomy for the purpose of controlling bleeding ndash Transfusion of ge5 U whole blood or packed red blood cells within a 48-hour period ndash Chest tube output 2 L within a 24-hour period
bull Type 5 ndash fatal bleeding bull Probable fatal bleeding (type 5a)
ndash bleeding that is clinically suspicious as the cause of death but the bleeding is not directly observed and there is no autopsy or confirmatory imaging
bull Definite fatal bleeding (type 5b) ndash bleeding that is directly observed (by either clinical specimen [blood
emesis stool etc] or imaging) or confirmed on autopsy
26 VCD
11
NSTEACS or STEMI with invasive management Aspirin+P2Y12 blocker
Trans-Femoral Access
Trans-Radial Access
To demonstrate that trans-radial intervention as
compared to femoral access site is associated to lower
rate of the composite endpoint of Death MI or Stroke
within the first 30 days
1deg co-Primary Objective
6 vs 42 βlt10 α 25 8200 patients
Adaptive study Design sample size (SS) will be increased
by the cross-over rate at 70 of planned SS
MATRIX Access site NCT01433627
MATRIX Access
39 93 132 200 276 380 490 685 857 1002 1190
1400 1684 1972 2248
2584 2926
3256 3560
3875 4144
4452 4726
5000 5322
5655 5896 6184
6458 6742 6982 7235 7444 7638 7844 8073
8404
Cumulative enrollment by month
8404
8404
8404 patients with ACS undergoing coronary angiography plusmn PCI from 11th Oct 2011 to 7th Nov 2014
Operator Eligibility Criteria Interventional cardiologist expertise in TRI and TFI including at least 75 transradial coronary interventions and at least 50 of interventions performed via radial route in the year preceding site initiation
Complete follow-up to 30 days available in 4183 (997) of radial and 4191 (99middot6) of femoral cohorts
Am Heart J 2014 Dec168(6)838-45e6
Cross Over and Procedural Success Rates
941 of radial and 974 of femoral cohorts received respective treatment as allocated
In 58 of radial and 23 of TF cohort the allocated access was attempted but failed
In 3 (01) in the radial and 13 (03) patients in the femoral groups the allocated access was not attempted
P=077 Plt0001
TIMI lt3 andor final stenosis gt30
88
103
15 significant reduction at nominal 5 alpha
which is however NOT significant at the pre-specificed
alpha of 25
Primary EP MACE
Femoral
Radial
Rate Ratio 083 95 CI 073 to 096 p=00092
117
98
NNTB 53 Femoral
Radial
Primary EP NACE
Mortalidad Total
IAM
Fatal and ST EPs All-Cause Cardiac non-CV mortality type of stent thrombosis
RR072
(053-099)
P=0045
RR 075
(054-104)
P=008 1
13
06
1
0
02
04
06
08
1
12
14
Radial Femoral
P=069
P=066
Mortality Stent Thrombosis
NNTB 167
Bleeding endpoints BARC TIMI GUSTO access vs non-access related
14
25
P=0013
RR 067 049-092
P=00004
RR 037 021-066
BARC 3 or 5
P=00098
RR 064 045-090
P=008
RR 072 050-104 P=020
RR 078 053-114
Major
or minor
moderate
or severe
P=082
P=068
Rardial Better Femoral Better 1
HAZARD RATIO (95 CI)
P-VALUES
Superiority Interaction
089 Intermediate (548-991)
075 (060-094)
104 (082-132) 076 0011
Centrersquos annual
volume of PCI
Low (247-544)
Intermediate (654-790)
Centrersquos
Proportion of
radial PCI
Low (149-644)
NSTE-ACS (tpndash) ACS type
STEMI
lt75 Age
ge75 023 088 (070-109)
082 (068-097) 0023 062
NACE Subgroup Analysis
High (1000-1950)
High (800-980)
NSTE-ACS (tp+)
Men Sex
Women
lt25 BMI
ge25
No
Ticagrelor or
prasugrel Yes
No Diabetes
Yes
lt60 GFR
ge60
No
History of
PVD Yes
2 025 050
075 (058-097) 0025
00048
101 (079-129)
095 (075 -122) 071
095
064 (051-080) lt0001
044
086 (068-108)
058 (033-103) 0059
019
085 (071-102) 007
0012 072 (056-093)
089 (076-105) 016 018
009 086 (073-102)
079 (063-099) 0038 053
007 083 (068-102)
084 (070-101) 006 094
045 091 (071-117)
080 (068-094) 008 043
001 078 (065-094)
086 (070-107) 018 051
060 091 (064-130)
083 (071-096) 0012 064
Radial Better Femoral Better 1
HAZARD RATIO (95 CI)
P-VALUES
Superiority Interaction
Intermediate (654-790)
Centrersquos
Proportion
of radial PCI
Low (149-644)
NSTE-ACS (tpndash) ACS
type
STEMI
Subgroup Analysis
High (800-980)
NSTE-ACS (tp+)
2
00157
128 (071-232)
069 (040 -119) 018
041
048 (028-081) 0006
010
087 (059-129) 049
049 (028-087) 0012
Intermediate (654-790) Centrersquos
Proportion
of radial PCI
Low (149-644)
NSTE-ACS (tpndash) ACS
type
STEMI
High (800-980)
NSTE-ACS (tp+)
020
090 (054-150)
057 (031 -103) 006
068
056 (032-097) 0035
054
062 (041-094)
166 (028-100) 058
0022
070 (042-117) 017
Mortality
Bleeding
4 050 025
1 2 050 025
Updated Meta-analysis 19328 ACS patients being randomly allocated to radial or femoral access
Rardial Better Femoral Better 1 4 025 050 2
Pre-Rival RIVAL Post-RIVAL MATRI
X Combined
Non-CABG
major bleeds
Death
myocardial
infarction or
stroke
Death
Myocardial
Infarction
Stroke
Pre-Rival RIVAL Post-RIVAL MATRI
X Combined
Pre-Rival RIVAL Post-RIVAL MATRI
X Combined
Pre-Rival RIVAL Post-RIVAL MATRI
X Combined
Pre-Rival RIVAL Post-RIVAL MATRI
X Combined
SUBGROUP Risk Ratio (95CI) P Value
Heterogenity
P Value I2
073 (043-123) 039 (023-067)
058 (046-072)
041 (022-076)
lt00001 0 05
1
067 (048-093) 086 (076-098) 086 (077-095)
098 (076-127)
00051 0 09
7
058 (039-087) 073 (053-099) 072 (060-088) 00011 0 10
0
085 (039-190) 091 (078-106) 091 (079-104)
092 (065-131)
01
6 0 08
8
068 (049-092)
082 (052-129)
077 (046-128) 086 (058-129)
073 (012-447)
140 (045-440) 100 (050-200) 105 (069-160)
143 (072-283)
08
0 0 07
5
026 (006-123)
Summary bull Among patients with an ACS with or without ST-segment
elevation who underwent invasive management the use
of radial access for coronary angiography plusmn PCI reduced
the rate of net adverse clinical events with a number
needed to treat for benefit of 53
ndash Differences between groups were driven by reductions in BARC
major bleeding unrelated to CABG and all-cause mortality with
radial access
bull Our results in conjunction with the updated meta-
analysis suggest that radial approach should
become the default access for patients with
ACS undergoing invasive management
Radial Acces 61000 menos Muertes
LA VIA TRANSRADIAL DEBERIA SER EL ACCESO DE ELECCION o ldquo DEFAULTrdquo PARA LOS PACIENTES CON SCA TRATADOS CON INTERVENCIONISMO PERCUTANEO
LA VIA TRANSRADIAL DEBERIA SER EL ACCESO DE ELECCION PARA TODO PACIENTE CONSIN SCA TRATADOS CON INTERVENCIONISMO PERCUTANEO
GRACIAS POR SU ATENCION
MACE
Mortality
No interaction between access and anticoagulant use in a post- hoc analysis of the subgroup of 7213 patients randomized to bivalirudin or unfractionated heparin for the two co-primary outcomes all-cause mortality or BARC 3 or 5 bleeding
Relevance of bleeding as a clinical endpoint
bull Availability of potent antithrombotic therapy including ndash ASA ndash P2Y12 inhibitors (clopidogrel prasugrel ticagrelor) ndash heparin ndash GP IIbIIIa inhibitors ndash direct thrombin inhibitors
bull has led to a reduction in ischemic events bull but is associated with an increased risk of
bleeding bull the increase in bleeding is associated with worse
clinical outcome
Rationale for a new bleeding definition
bull Increased importance of bleeding as prognostic factor
bull Need for assessment of bleeding in RCTs and registries
bull Lack of comparability bull Need for standardized definitions to avoid
erroneous conclusions
ndash regarding safety of a given agent ndash regarding superiority of one agent over another
Open questions regarding BARC
bull Why 48-hour window for CABG-related bleeding
bull Why type 1 bdquonot actionableldquo when patient may bdquotake actionldquo such as discontinuing medication (with potentially serious consequences such as ST)
bull Why consider intraocular bleed equivalent to intracranial bleed for BARC 3c
bull Type 1 bleed subject to misinterpretation by the patient
Hicks et al (editorial) Circulation 20111232664
Conclusion
bull BARC is a new objective hierarchically graded classification of bleeding
(Mehran Circulation [June 14] 20111232736)
bull BARC is based on consensus rather than data-driven
bull Prospective validation is warranted ndash across the spectrum of IHD
ndash across management strategies (conservative invasive)
ndash in the context of all invasive procedures (PCI CABG endovascular TAVI)
Conclusion (2)
bull Final validation of BARC and proof of its utility depend on
ndash its use by all future RCTs as common safety endpoint
ndash unanimous assessment procedure (questionnaires)
bull More important than using one or the other bleeding risk score is the agreement and commitment among clinical trialists to use the same score for comparability of data
BARC (Bleeding Academic Research Consortium) definitions
Mehran et al Circulation 20111232736-2747
bull Type 3 clinical laboratory andor imaging evidence of bleeding with healthcare provider responses ndash BARC type 3a
bull any transfusion with overt bleeding bull overt bleeding plus hemoglobin drop ge3 to lt5 gdL
ndash BARC type 3b bull overt bleeding plus hemoglobin drop gt5 gdL bull Cardiac tamponade bull Bleeding requiring surgical intervention for control (excluding dentalnasalskinhemorrhoid) bull Bleeding requiring intravenous vasoactive drugs
ndash BARC type 3c bull Intracranial hemorrhage subcategories confirmed by autopsy
imaging or lumbar puncture bull Intraocular bleed compromising vision
BARC Bleeding Academic Research Consortium) definitions
Mehran et al Circulation 20111232736-2747
bull Type 4 Coronary Artery Bypass Graftndashrelated bleeding ndash Perioperative intracranial bleeding within 48 hours ndash Reoperation after closure of sternotomy for the purpose of controlling bleeding ndash Transfusion of ge5 U whole blood or packed red blood cells within a 48-hour period ndash Chest tube output 2 L within a 24-hour period
bull Type 5 ndash fatal bleeding bull Probable fatal bleeding (type 5a)
ndash bleeding that is clinically suspicious as the cause of death but the bleeding is not directly observed and there is no autopsy or confirmatory imaging
bull Definite fatal bleeding (type 5b) ndash bleeding that is directly observed (by either clinical specimen [blood
emesis stool etc] or imaging) or confirmed on autopsy
26 VCD
11
NSTEACS or STEMI with invasive management Aspirin+P2Y12 blocker
Trans-Femoral Access
Trans-Radial Access
To demonstrate that trans-radial intervention as
compared to femoral access site is associated to lower
rate of the composite endpoint of Death MI or Stroke
within the first 30 days
1deg co-Primary Objective
6 vs 42 βlt10 α 25 8200 patients
Adaptive study Design sample size (SS) will be increased
by the cross-over rate at 70 of planned SS
MATRIX Access site NCT01433627
MATRIX Access
39 93 132 200 276 380 490 685 857 1002 1190
1400 1684 1972 2248
2584 2926
3256 3560
3875 4144
4452 4726
5000 5322
5655 5896 6184
6458 6742 6982 7235 7444 7638 7844 8073
8404
Cumulative enrollment by month
8404
8404
8404 patients with ACS undergoing coronary angiography plusmn PCI from 11th Oct 2011 to 7th Nov 2014
Operator Eligibility Criteria Interventional cardiologist expertise in TRI and TFI including at least 75 transradial coronary interventions and at least 50 of interventions performed via radial route in the year preceding site initiation
Complete follow-up to 30 days available in 4183 (997) of radial and 4191 (99middot6) of femoral cohorts
Am Heart J 2014 Dec168(6)838-45e6
Cross Over and Procedural Success Rates
941 of radial and 974 of femoral cohorts received respective treatment as allocated
In 58 of radial and 23 of TF cohort the allocated access was attempted but failed
In 3 (01) in the radial and 13 (03) patients in the femoral groups the allocated access was not attempted
P=077 Plt0001
TIMI lt3 andor final stenosis gt30
88
103
15 significant reduction at nominal 5 alpha
which is however NOT significant at the pre-specificed
alpha of 25
Primary EP MACE
Femoral
Radial
Rate Ratio 083 95 CI 073 to 096 p=00092
117
98
NNTB 53 Femoral
Radial
Primary EP NACE
Mortalidad Total
IAM
Fatal and ST EPs All-Cause Cardiac non-CV mortality type of stent thrombosis
RR072
(053-099)
P=0045
RR 075
(054-104)
P=008 1
13
06
1
0
02
04
06
08
1
12
14
Radial Femoral
P=069
P=066
Mortality Stent Thrombosis
NNTB 167
Bleeding endpoints BARC TIMI GUSTO access vs non-access related
14
25
P=0013
RR 067 049-092
P=00004
RR 037 021-066
BARC 3 or 5
P=00098
RR 064 045-090
P=008
RR 072 050-104 P=020
RR 078 053-114
Major
or minor
moderate
or severe
P=082
P=068
Rardial Better Femoral Better 1
HAZARD RATIO (95 CI)
P-VALUES
Superiority Interaction
089 Intermediate (548-991)
075 (060-094)
104 (082-132) 076 0011
Centrersquos annual
volume of PCI
Low (247-544)
Intermediate (654-790)
Centrersquos
Proportion of
radial PCI
Low (149-644)
NSTE-ACS (tpndash) ACS type
STEMI
lt75 Age
ge75 023 088 (070-109)
082 (068-097) 0023 062
NACE Subgroup Analysis
High (1000-1950)
High (800-980)
NSTE-ACS (tp+)
Men Sex
Women
lt25 BMI
ge25
No
Ticagrelor or
prasugrel Yes
No Diabetes
Yes
lt60 GFR
ge60
No
History of
PVD Yes
2 025 050
075 (058-097) 0025
00048
101 (079-129)
095 (075 -122) 071
095
064 (051-080) lt0001
044
086 (068-108)
058 (033-103) 0059
019
085 (071-102) 007
0012 072 (056-093)
089 (076-105) 016 018
009 086 (073-102)
079 (063-099) 0038 053
007 083 (068-102)
084 (070-101) 006 094
045 091 (071-117)
080 (068-094) 008 043
001 078 (065-094)
086 (070-107) 018 051
060 091 (064-130)
083 (071-096) 0012 064
Radial Better Femoral Better 1
HAZARD RATIO (95 CI)
P-VALUES
Superiority Interaction
Intermediate (654-790)
Centrersquos
Proportion
of radial PCI
Low (149-644)
NSTE-ACS (tpndash) ACS
type
STEMI
Subgroup Analysis
High (800-980)
NSTE-ACS (tp+)
2
00157
128 (071-232)
069 (040 -119) 018
041
048 (028-081) 0006
010
087 (059-129) 049
049 (028-087) 0012
Intermediate (654-790) Centrersquos
Proportion
of radial PCI
Low (149-644)
NSTE-ACS (tpndash) ACS
type
STEMI
High (800-980)
NSTE-ACS (tp+)
020
090 (054-150)
057 (031 -103) 006
068
056 (032-097) 0035
054
062 (041-094)
166 (028-100) 058
0022
070 (042-117) 017
Mortality
Bleeding
4 050 025
1 2 050 025
Updated Meta-analysis 19328 ACS patients being randomly allocated to radial or femoral access
Rardial Better Femoral Better 1 4 025 050 2
Pre-Rival RIVAL Post-RIVAL MATRI
X Combined
Non-CABG
major bleeds
Death
myocardial
infarction or
stroke
Death
Myocardial
Infarction
Stroke
Pre-Rival RIVAL Post-RIVAL MATRI
X Combined
Pre-Rival RIVAL Post-RIVAL MATRI
X Combined
Pre-Rival RIVAL Post-RIVAL MATRI
X Combined
Pre-Rival RIVAL Post-RIVAL MATRI
X Combined
SUBGROUP Risk Ratio (95CI) P Value
Heterogenity
P Value I2
073 (043-123) 039 (023-067)
058 (046-072)
041 (022-076)
lt00001 0 05
1
067 (048-093) 086 (076-098) 086 (077-095)
098 (076-127)
00051 0 09
7
058 (039-087) 073 (053-099) 072 (060-088) 00011 0 10
0
085 (039-190) 091 (078-106) 091 (079-104)
092 (065-131)
01
6 0 08
8
068 (049-092)
082 (052-129)
077 (046-128) 086 (058-129)
073 (012-447)
140 (045-440) 100 (050-200) 105 (069-160)
143 (072-283)
08
0 0 07
5
026 (006-123)
Summary bull Among patients with an ACS with or without ST-segment
elevation who underwent invasive management the use
of radial access for coronary angiography plusmn PCI reduced
the rate of net adverse clinical events with a number
needed to treat for benefit of 53
ndash Differences between groups were driven by reductions in BARC
major bleeding unrelated to CABG and all-cause mortality with
radial access
bull Our results in conjunction with the updated meta-
analysis suggest that radial approach should
become the default access for patients with
ACS undergoing invasive management
Radial Acces 61000 menos Muertes
LA VIA TRANSRADIAL DEBERIA SER EL ACCESO DE ELECCION o ldquo DEFAULTrdquo PARA LOS PACIENTES CON SCA TRATADOS CON INTERVENCIONISMO PERCUTANEO
LA VIA TRANSRADIAL DEBERIA SER EL ACCESO DE ELECCION PARA TODO PACIENTE CONSIN SCA TRATADOS CON INTERVENCIONISMO PERCUTANEO
GRACIAS POR SU ATENCION
MACE
Mortality
No interaction between access and anticoagulant use in a post- hoc analysis of the subgroup of 7213 patients randomized to bivalirudin or unfractionated heparin for the two co-primary outcomes all-cause mortality or BARC 3 or 5 bleeding
Relevance of bleeding as a clinical endpoint
bull Availability of potent antithrombotic therapy including ndash ASA ndash P2Y12 inhibitors (clopidogrel prasugrel ticagrelor) ndash heparin ndash GP IIbIIIa inhibitors ndash direct thrombin inhibitors
bull has led to a reduction in ischemic events bull but is associated with an increased risk of
bleeding bull the increase in bleeding is associated with worse
clinical outcome
Rationale for a new bleeding definition
bull Increased importance of bleeding as prognostic factor
bull Need for assessment of bleeding in RCTs and registries
bull Lack of comparability bull Need for standardized definitions to avoid
erroneous conclusions
ndash regarding safety of a given agent ndash regarding superiority of one agent over another
Open questions regarding BARC
bull Why 48-hour window for CABG-related bleeding
bull Why type 1 bdquonot actionableldquo when patient may bdquotake actionldquo such as discontinuing medication (with potentially serious consequences such as ST)
bull Why consider intraocular bleed equivalent to intracranial bleed for BARC 3c
bull Type 1 bleed subject to misinterpretation by the patient
Hicks et al (editorial) Circulation 20111232664
Conclusion
bull BARC is a new objective hierarchically graded classification of bleeding
(Mehran Circulation [June 14] 20111232736)
bull BARC is based on consensus rather than data-driven
bull Prospective validation is warranted ndash across the spectrum of IHD
ndash across management strategies (conservative invasive)
ndash in the context of all invasive procedures (PCI CABG endovascular TAVI)
Conclusion (2)
bull Final validation of BARC and proof of its utility depend on
ndash its use by all future RCTs as common safety endpoint
ndash unanimous assessment procedure (questionnaires)
bull More important than using one or the other bleeding risk score is the agreement and commitment among clinical trialists to use the same score for comparability of data
BARC Bleeding Academic Research Consortium) definitions
Mehran et al Circulation 20111232736-2747
bull Type 4 Coronary Artery Bypass Graftndashrelated bleeding ndash Perioperative intracranial bleeding within 48 hours ndash Reoperation after closure of sternotomy for the purpose of controlling bleeding ndash Transfusion of ge5 U whole blood or packed red blood cells within a 48-hour period ndash Chest tube output 2 L within a 24-hour period
bull Type 5 ndash fatal bleeding bull Probable fatal bleeding (type 5a)
ndash bleeding that is clinically suspicious as the cause of death but the bleeding is not directly observed and there is no autopsy or confirmatory imaging
bull Definite fatal bleeding (type 5b) ndash bleeding that is directly observed (by either clinical specimen [blood
emesis stool etc] or imaging) or confirmed on autopsy
26 VCD
11
NSTEACS or STEMI with invasive management Aspirin+P2Y12 blocker
Trans-Femoral Access
Trans-Radial Access
To demonstrate that trans-radial intervention as
compared to femoral access site is associated to lower
rate of the composite endpoint of Death MI or Stroke
within the first 30 days
1deg co-Primary Objective
6 vs 42 βlt10 α 25 8200 patients
Adaptive study Design sample size (SS) will be increased
by the cross-over rate at 70 of planned SS
MATRIX Access site NCT01433627
MATRIX Access
39 93 132 200 276 380 490 685 857 1002 1190
1400 1684 1972 2248
2584 2926
3256 3560
3875 4144
4452 4726
5000 5322
5655 5896 6184
6458 6742 6982 7235 7444 7638 7844 8073
8404
Cumulative enrollment by month
8404
8404
8404 patients with ACS undergoing coronary angiography plusmn PCI from 11th Oct 2011 to 7th Nov 2014
Operator Eligibility Criteria Interventional cardiologist expertise in TRI and TFI including at least 75 transradial coronary interventions and at least 50 of interventions performed via radial route in the year preceding site initiation
Complete follow-up to 30 days available in 4183 (997) of radial and 4191 (99middot6) of femoral cohorts
Am Heart J 2014 Dec168(6)838-45e6
Cross Over and Procedural Success Rates
941 of radial and 974 of femoral cohorts received respective treatment as allocated
In 58 of radial and 23 of TF cohort the allocated access was attempted but failed
In 3 (01) in the radial and 13 (03) patients in the femoral groups the allocated access was not attempted
P=077 Plt0001
TIMI lt3 andor final stenosis gt30
88
103
15 significant reduction at nominal 5 alpha
which is however NOT significant at the pre-specificed
alpha of 25
Primary EP MACE
Femoral
Radial
Rate Ratio 083 95 CI 073 to 096 p=00092
117
98
NNTB 53 Femoral
Radial
Primary EP NACE
Mortalidad Total
IAM
Fatal and ST EPs All-Cause Cardiac non-CV mortality type of stent thrombosis
RR072
(053-099)
P=0045
RR 075
(054-104)
P=008 1
13
06
1
0
02
04
06
08
1
12
14
Radial Femoral
P=069
P=066
Mortality Stent Thrombosis
NNTB 167
Bleeding endpoints BARC TIMI GUSTO access vs non-access related
14
25
P=0013
RR 067 049-092
P=00004
RR 037 021-066
BARC 3 or 5
P=00098
RR 064 045-090
P=008
RR 072 050-104 P=020
RR 078 053-114
Major
or minor
moderate
or severe
P=082
P=068
Rardial Better Femoral Better 1
HAZARD RATIO (95 CI)
P-VALUES
Superiority Interaction
089 Intermediate (548-991)
075 (060-094)
104 (082-132) 076 0011
Centrersquos annual
volume of PCI
Low (247-544)
Intermediate (654-790)
Centrersquos
Proportion of
radial PCI
Low (149-644)
NSTE-ACS (tpndash) ACS type
STEMI
lt75 Age
ge75 023 088 (070-109)
082 (068-097) 0023 062
NACE Subgroup Analysis
High (1000-1950)
High (800-980)
NSTE-ACS (tp+)
Men Sex
Women
lt25 BMI
ge25
No
Ticagrelor or
prasugrel Yes
No Diabetes
Yes
lt60 GFR
ge60
No
History of
PVD Yes
2 025 050
075 (058-097) 0025
00048
101 (079-129)
095 (075 -122) 071
095
064 (051-080) lt0001
044
086 (068-108)
058 (033-103) 0059
019
085 (071-102) 007
0012 072 (056-093)
089 (076-105) 016 018
009 086 (073-102)
079 (063-099) 0038 053
007 083 (068-102)
084 (070-101) 006 094
045 091 (071-117)
080 (068-094) 008 043
001 078 (065-094)
086 (070-107) 018 051
060 091 (064-130)
083 (071-096) 0012 064
Radial Better Femoral Better 1
HAZARD RATIO (95 CI)
P-VALUES
Superiority Interaction
Intermediate (654-790)
Centrersquos
Proportion
of radial PCI
Low (149-644)
NSTE-ACS (tpndash) ACS
type
STEMI
Subgroup Analysis
High (800-980)
NSTE-ACS (tp+)
2
00157
128 (071-232)
069 (040 -119) 018
041
048 (028-081) 0006
010
087 (059-129) 049
049 (028-087) 0012
Intermediate (654-790) Centrersquos
Proportion
of radial PCI
Low (149-644)
NSTE-ACS (tpndash) ACS
type
STEMI
High (800-980)
NSTE-ACS (tp+)
020
090 (054-150)
057 (031 -103) 006
068
056 (032-097) 0035
054
062 (041-094)
166 (028-100) 058
0022
070 (042-117) 017
Mortality
Bleeding
4 050 025
1 2 050 025
Updated Meta-analysis 19328 ACS patients being randomly allocated to radial or femoral access
Rardial Better Femoral Better 1 4 025 050 2
Pre-Rival RIVAL Post-RIVAL MATRI
X Combined
Non-CABG
major bleeds
Death
myocardial
infarction or
stroke
Death
Myocardial
Infarction
Stroke
Pre-Rival RIVAL Post-RIVAL MATRI
X Combined
Pre-Rival RIVAL Post-RIVAL MATRI
X Combined
Pre-Rival RIVAL Post-RIVAL MATRI
X Combined
Pre-Rival RIVAL Post-RIVAL MATRI
X Combined
SUBGROUP Risk Ratio (95CI) P Value
Heterogenity
P Value I2
073 (043-123) 039 (023-067)
058 (046-072)
041 (022-076)
lt00001 0 05
1
067 (048-093) 086 (076-098) 086 (077-095)
098 (076-127)
00051 0 09
7
058 (039-087) 073 (053-099) 072 (060-088) 00011 0 10
0
085 (039-190) 091 (078-106) 091 (079-104)
092 (065-131)
01
6 0 08
8
068 (049-092)
082 (052-129)
077 (046-128) 086 (058-129)
073 (012-447)
140 (045-440) 100 (050-200) 105 (069-160)
143 (072-283)
08
0 0 07
5
026 (006-123)
Summary bull Among patients with an ACS with or without ST-segment
elevation who underwent invasive management the use
of radial access for coronary angiography plusmn PCI reduced
the rate of net adverse clinical events with a number
needed to treat for benefit of 53
ndash Differences between groups were driven by reductions in BARC
major bleeding unrelated to CABG and all-cause mortality with
radial access
bull Our results in conjunction with the updated meta-
analysis suggest that radial approach should
become the default access for patients with
ACS undergoing invasive management
Radial Acces 61000 menos Muertes
LA VIA TRANSRADIAL DEBERIA SER EL ACCESO DE ELECCION o ldquo DEFAULTrdquo PARA LOS PACIENTES CON SCA TRATADOS CON INTERVENCIONISMO PERCUTANEO
LA VIA TRANSRADIAL DEBERIA SER EL ACCESO DE ELECCION PARA TODO PACIENTE CONSIN SCA TRATADOS CON INTERVENCIONISMO PERCUTANEO
GRACIAS POR SU ATENCION
MACE
Mortality
No interaction between access and anticoagulant use in a post- hoc analysis of the subgroup of 7213 patients randomized to bivalirudin or unfractionated heparin for the two co-primary outcomes all-cause mortality or BARC 3 or 5 bleeding
Relevance of bleeding as a clinical endpoint
bull Availability of potent antithrombotic therapy including ndash ASA ndash P2Y12 inhibitors (clopidogrel prasugrel ticagrelor) ndash heparin ndash GP IIbIIIa inhibitors ndash direct thrombin inhibitors
bull has led to a reduction in ischemic events bull but is associated with an increased risk of
bleeding bull the increase in bleeding is associated with worse
clinical outcome
Rationale for a new bleeding definition
bull Increased importance of bleeding as prognostic factor
bull Need for assessment of bleeding in RCTs and registries
bull Lack of comparability bull Need for standardized definitions to avoid
erroneous conclusions
ndash regarding safety of a given agent ndash regarding superiority of one agent over another
Open questions regarding BARC
bull Why 48-hour window for CABG-related bleeding
bull Why type 1 bdquonot actionableldquo when patient may bdquotake actionldquo such as discontinuing medication (with potentially serious consequences such as ST)
bull Why consider intraocular bleed equivalent to intracranial bleed for BARC 3c
bull Type 1 bleed subject to misinterpretation by the patient
Hicks et al (editorial) Circulation 20111232664
Conclusion
bull BARC is a new objective hierarchically graded classification of bleeding
(Mehran Circulation [June 14] 20111232736)
bull BARC is based on consensus rather than data-driven
bull Prospective validation is warranted ndash across the spectrum of IHD
ndash across management strategies (conservative invasive)
ndash in the context of all invasive procedures (PCI CABG endovascular TAVI)
Conclusion (2)
bull Final validation of BARC and proof of its utility depend on
ndash its use by all future RCTs as common safety endpoint
ndash unanimous assessment procedure (questionnaires)
bull More important than using one or the other bleeding risk score is the agreement and commitment among clinical trialists to use the same score for comparability of data
26 VCD
11
NSTEACS or STEMI with invasive management Aspirin+P2Y12 blocker
Trans-Femoral Access
Trans-Radial Access
To demonstrate that trans-radial intervention as
compared to femoral access site is associated to lower
rate of the composite endpoint of Death MI or Stroke
within the first 30 days
1deg co-Primary Objective
6 vs 42 βlt10 α 25 8200 patients
Adaptive study Design sample size (SS) will be increased
by the cross-over rate at 70 of planned SS
MATRIX Access site NCT01433627
MATRIX Access
39 93 132 200 276 380 490 685 857 1002 1190
1400 1684 1972 2248
2584 2926
3256 3560
3875 4144
4452 4726
5000 5322
5655 5896 6184
6458 6742 6982 7235 7444 7638 7844 8073
8404
Cumulative enrollment by month
8404
8404
8404 patients with ACS undergoing coronary angiography plusmn PCI from 11th Oct 2011 to 7th Nov 2014
Operator Eligibility Criteria Interventional cardiologist expertise in TRI and TFI including at least 75 transradial coronary interventions and at least 50 of interventions performed via radial route in the year preceding site initiation
Complete follow-up to 30 days available in 4183 (997) of radial and 4191 (99middot6) of femoral cohorts
Am Heart J 2014 Dec168(6)838-45e6
Cross Over and Procedural Success Rates
941 of radial and 974 of femoral cohorts received respective treatment as allocated
In 58 of radial and 23 of TF cohort the allocated access was attempted but failed
In 3 (01) in the radial and 13 (03) patients in the femoral groups the allocated access was not attempted
P=077 Plt0001
TIMI lt3 andor final stenosis gt30
88
103
15 significant reduction at nominal 5 alpha
which is however NOT significant at the pre-specificed
alpha of 25
Primary EP MACE
Femoral
Radial
Rate Ratio 083 95 CI 073 to 096 p=00092
117
98
NNTB 53 Femoral
Radial
Primary EP NACE
Mortalidad Total
IAM
Fatal and ST EPs All-Cause Cardiac non-CV mortality type of stent thrombosis
RR072
(053-099)
P=0045
RR 075
(054-104)
P=008 1
13
06
1
0
02
04
06
08
1
12
14
Radial Femoral
P=069
P=066
Mortality Stent Thrombosis
NNTB 167
Bleeding endpoints BARC TIMI GUSTO access vs non-access related
14
25
P=0013
RR 067 049-092
P=00004
RR 037 021-066
BARC 3 or 5
P=00098
RR 064 045-090
P=008
RR 072 050-104 P=020
RR 078 053-114
Major
or minor
moderate
or severe
P=082
P=068
Rardial Better Femoral Better 1
HAZARD RATIO (95 CI)
P-VALUES
Superiority Interaction
089 Intermediate (548-991)
075 (060-094)
104 (082-132) 076 0011
Centrersquos annual
volume of PCI
Low (247-544)
Intermediate (654-790)
Centrersquos
Proportion of
radial PCI
Low (149-644)
NSTE-ACS (tpndash) ACS type
STEMI
lt75 Age
ge75 023 088 (070-109)
082 (068-097) 0023 062
NACE Subgroup Analysis
High (1000-1950)
High (800-980)
NSTE-ACS (tp+)
Men Sex
Women
lt25 BMI
ge25
No
Ticagrelor or
prasugrel Yes
No Diabetes
Yes
lt60 GFR
ge60
No
History of
PVD Yes
2 025 050
075 (058-097) 0025
00048
101 (079-129)
095 (075 -122) 071
095
064 (051-080) lt0001
044
086 (068-108)
058 (033-103) 0059
019
085 (071-102) 007
0012 072 (056-093)
089 (076-105) 016 018
009 086 (073-102)
079 (063-099) 0038 053
007 083 (068-102)
084 (070-101) 006 094
045 091 (071-117)
080 (068-094) 008 043
001 078 (065-094)
086 (070-107) 018 051
060 091 (064-130)
083 (071-096) 0012 064
Radial Better Femoral Better 1
HAZARD RATIO (95 CI)
P-VALUES
Superiority Interaction
Intermediate (654-790)
Centrersquos
Proportion
of radial PCI
Low (149-644)
NSTE-ACS (tpndash) ACS
type
STEMI
Subgroup Analysis
High (800-980)
NSTE-ACS (tp+)
2
00157
128 (071-232)
069 (040 -119) 018
041
048 (028-081) 0006
010
087 (059-129) 049
049 (028-087) 0012
Intermediate (654-790) Centrersquos
Proportion
of radial PCI
Low (149-644)
NSTE-ACS (tpndash) ACS
type
STEMI
High (800-980)
NSTE-ACS (tp+)
020
090 (054-150)
057 (031 -103) 006
068
056 (032-097) 0035
054
062 (041-094)
166 (028-100) 058
0022
070 (042-117) 017
Mortality
Bleeding
4 050 025
1 2 050 025
Updated Meta-analysis 19328 ACS patients being randomly allocated to radial or femoral access
Rardial Better Femoral Better 1 4 025 050 2
Pre-Rival RIVAL Post-RIVAL MATRI
X Combined
Non-CABG
major bleeds
Death
myocardial
infarction or
stroke
Death
Myocardial
Infarction
Stroke
Pre-Rival RIVAL Post-RIVAL MATRI
X Combined
Pre-Rival RIVAL Post-RIVAL MATRI
X Combined
Pre-Rival RIVAL Post-RIVAL MATRI
X Combined
Pre-Rival RIVAL Post-RIVAL MATRI
X Combined
SUBGROUP Risk Ratio (95CI) P Value
Heterogenity
P Value I2
073 (043-123) 039 (023-067)
058 (046-072)
041 (022-076)
lt00001 0 05
1
067 (048-093) 086 (076-098) 086 (077-095)
098 (076-127)
00051 0 09
7
058 (039-087) 073 (053-099) 072 (060-088) 00011 0 10
0
085 (039-190) 091 (078-106) 091 (079-104)
092 (065-131)
01
6 0 08
8
068 (049-092)
082 (052-129)
077 (046-128) 086 (058-129)
073 (012-447)
140 (045-440) 100 (050-200) 105 (069-160)
143 (072-283)
08
0 0 07
5
026 (006-123)
Summary bull Among patients with an ACS with or without ST-segment
elevation who underwent invasive management the use
of radial access for coronary angiography plusmn PCI reduced
the rate of net adverse clinical events with a number
needed to treat for benefit of 53
ndash Differences between groups were driven by reductions in BARC
major bleeding unrelated to CABG and all-cause mortality with
radial access
bull Our results in conjunction with the updated meta-
analysis suggest that radial approach should
become the default access for patients with
ACS undergoing invasive management
Radial Acces 61000 menos Muertes
LA VIA TRANSRADIAL DEBERIA SER EL ACCESO DE ELECCION o ldquo DEFAULTrdquo PARA LOS PACIENTES CON SCA TRATADOS CON INTERVENCIONISMO PERCUTANEO
LA VIA TRANSRADIAL DEBERIA SER EL ACCESO DE ELECCION PARA TODO PACIENTE CONSIN SCA TRATADOS CON INTERVENCIONISMO PERCUTANEO
GRACIAS POR SU ATENCION
MACE
Mortality
No interaction between access and anticoagulant use in a post- hoc analysis of the subgroup of 7213 patients randomized to bivalirudin or unfractionated heparin for the two co-primary outcomes all-cause mortality or BARC 3 or 5 bleeding
Relevance of bleeding as a clinical endpoint
bull Availability of potent antithrombotic therapy including ndash ASA ndash P2Y12 inhibitors (clopidogrel prasugrel ticagrelor) ndash heparin ndash GP IIbIIIa inhibitors ndash direct thrombin inhibitors
bull has led to a reduction in ischemic events bull but is associated with an increased risk of
bleeding bull the increase in bleeding is associated with worse
clinical outcome
Rationale for a new bleeding definition
bull Increased importance of bleeding as prognostic factor
bull Need for assessment of bleeding in RCTs and registries
bull Lack of comparability bull Need for standardized definitions to avoid
erroneous conclusions
ndash regarding safety of a given agent ndash regarding superiority of one agent over another
Open questions regarding BARC
bull Why 48-hour window for CABG-related bleeding
bull Why type 1 bdquonot actionableldquo when patient may bdquotake actionldquo such as discontinuing medication (with potentially serious consequences such as ST)
bull Why consider intraocular bleed equivalent to intracranial bleed for BARC 3c
bull Type 1 bleed subject to misinterpretation by the patient
Hicks et al (editorial) Circulation 20111232664
Conclusion
bull BARC is a new objective hierarchically graded classification of bleeding
(Mehran Circulation [June 14] 20111232736)
bull BARC is based on consensus rather than data-driven
bull Prospective validation is warranted ndash across the spectrum of IHD
ndash across management strategies (conservative invasive)
ndash in the context of all invasive procedures (PCI CABG endovascular TAVI)
Conclusion (2)
bull Final validation of BARC and proof of its utility depend on
ndash its use by all future RCTs as common safety endpoint
ndash unanimous assessment procedure (questionnaires)
bull More important than using one or the other bleeding risk score is the agreement and commitment among clinical trialists to use the same score for comparability of data
11
NSTEACS or STEMI with invasive management Aspirin+P2Y12 blocker
Trans-Femoral Access
Trans-Radial Access
To demonstrate that trans-radial intervention as
compared to femoral access site is associated to lower
rate of the composite endpoint of Death MI or Stroke
within the first 30 days
1deg co-Primary Objective
6 vs 42 βlt10 α 25 8200 patients
Adaptive study Design sample size (SS) will be increased
by the cross-over rate at 70 of planned SS
MATRIX Access site NCT01433627
MATRIX Access
39 93 132 200 276 380 490 685 857 1002 1190
1400 1684 1972 2248
2584 2926
3256 3560
3875 4144
4452 4726
5000 5322
5655 5896 6184
6458 6742 6982 7235 7444 7638 7844 8073
8404
Cumulative enrollment by month
8404
8404
8404 patients with ACS undergoing coronary angiography plusmn PCI from 11th Oct 2011 to 7th Nov 2014
Operator Eligibility Criteria Interventional cardiologist expertise in TRI and TFI including at least 75 transradial coronary interventions and at least 50 of interventions performed via radial route in the year preceding site initiation
Complete follow-up to 30 days available in 4183 (997) of radial and 4191 (99middot6) of femoral cohorts
Am Heart J 2014 Dec168(6)838-45e6
Cross Over and Procedural Success Rates
941 of radial and 974 of femoral cohorts received respective treatment as allocated
In 58 of radial and 23 of TF cohort the allocated access was attempted but failed
In 3 (01) in the radial and 13 (03) patients in the femoral groups the allocated access was not attempted
P=077 Plt0001
TIMI lt3 andor final stenosis gt30
88
103
15 significant reduction at nominal 5 alpha
which is however NOT significant at the pre-specificed
alpha of 25
Primary EP MACE
Femoral
Radial
Rate Ratio 083 95 CI 073 to 096 p=00092
117
98
NNTB 53 Femoral
Radial
Primary EP NACE
Mortalidad Total
IAM
Fatal and ST EPs All-Cause Cardiac non-CV mortality type of stent thrombosis
RR072
(053-099)
P=0045
RR 075
(054-104)
P=008 1
13
06
1
0
02
04
06
08
1
12
14
Radial Femoral
P=069
P=066
Mortality Stent Thrombosis
NNTB 167
Bleeding endpoints BARC TIMI GUSTO access vs non-access related
14
25
P=0013
RR 067 049-092
P=00004
RR 037 021-066
BARC 3 or 5
P=00098
RR 064 045-090
P=008
RR 072 050-104 P=020
RR 078 053-114
Major
or minor
moderate
or severe
P=082
P=068
Rardial Better Femoral Better 1
HAZARD RATIO (95 CI)
P-VALUES
Superiority Interaction
089 Intermediate (548-991)
075 (060-094)
104 (082-132) 076 0011
Centrersquos annual
volume of PCI
Low (247-544)
Intermediate (654-790)
Centrersquos
Proportion of
radial PCI
Low (149-644)
NSTE-ACS (tpndash) ACS type
STEMI
lt75 Age
ge75 023 088 (070-109)
082 (068-097) 0023 062
NACE Subgroup Analysis
High (1000-1950)
High (800-980)
NSTE-ACS (tp+)
Men Sex
Women
lt25 BMI
ge25
No
Ticagrelor or
prasugrel Yes
No Diabetes
Yes
lt60 GFR
ge60
No
History of
PVD Yes
2 025 050
075 (058-097) 0025
00048
101 (079-129)
095 (075 -122) 071
095
064 (051-080) lt0001
044
086 (068-108)
058 (033-103) 0059
019
085 (071-102) 007
0012 072 (056-093)
089 (076-105) 016 018
009 086 (073-102)
079 (063-099) 0038 053
007 083 (068-102)
084 (070-101) 006 094
045 091 (071-117)
080 (068-094) 008 043
001 078 (065-094)
086 (070-107) 018 051
060 091 (064-130)
083 (071-096) 0012 064
Radial Better Femoral Better 1
HAZARD RATIO (95 CI)
P-VALUES
Superiority Interaction
Intermediate (654-790)
Centrersquos
Proportion
of radial PCI
Low (149-644)
NSTE-ACS (tpndash) ACS
type
STEMI
Subgroup Analysis
High (800-980)
NSTE-ACS (tp+)
2
00157
128 (071-232)
069 (040 -119) 018
041
048 (028-081) 0006
010
087 (059-129) 049
049 (028-087) 0012
Intermediate (654-790) Centrersquos
Proportion
of radial PCI
Low (149-644)
NSTE-ACS (tpndash) ACS
type
STEMI
High (800-980)
NSTE-ACS (tp+)
020
090 (054-150)
057 (031 -103) 006
068
056 (032-097) 0035
054
062 (041-094)
166 (028-100) 058
0022
070 (042-117) 017
Mortality
Bleeding
4 050 025
1 2 050 025
Updated Meta-analysis 19328 ACS patients being randomly allocated to radial or femoral access
Rardial Better Femoral Better 1 4 025 050 2
Pre-Rival RIVAL Post-RIVAL MATRI
X Combined
Non-CABG
major bleeds
Death
myocardial
infarction or
stroke
Death
Myocardial
Infarction
Stroke
Pre-Rival RIVAL Post-RIVAL MATRI
X Combined
Pre-Rival RIVAL Post-RIVAL MATRI
X Combined
Pre-Rival RIVAL Post-RIVAL MATRI
X Combined
Pre-Rival RIVAL Post-RIVAL MATRI
X Combined
SUBGROUP Risk Ratio (95CI) P Value
Heterogenity
P Value I2
073 (043-123) 039 (023-067)
058 (046-072)
041 (022-076)
lt00001 0 05
1
067 (048-093) 086 (076-098) 086 (077-095)
098 (076-127)
00051 0 09
7
058 (039-087) 073 (053-099) 072 (060-088) 00011 0 10
0
085 (039-190) 091 (078-106) 091 (079-104)
092 (065-131)
01
6 0 08
8
068 (049-092)
082 (052-129)
077 (046-128) 086 (058-129)
073 (012-447)
140 (045-440) 100 (050-200) 105 (069-160)
143 (072-283)
08
0 0 07
5
026 (006-123)
Summary bull Among patients with an ACS with or without ST-segment
elevation who underwent invasive management the use
of radial access for coronary angiography plusmn PCI reduced
the rate of net adverse clinical events with a number
needed to treat for benefit of 53
ndash Differences between groups were driven by reductions in BARC
major bleeding unrelated to CABG and all-cause mortality with
radial access
bull Our results in conjunction with the updated meta-
analysis suggest that radial approach should
become the default access for patients with
ACS undergoing invasive management
Radial Acces 61000 menos Muertes
LA VIA TRANSRADIAL DEBERIA SER EL ACCESO DE ELECCION o ldquo DEFAULTrdquo PARA LOS PACIENTES CON SCA TRATADOS CON INTERVENCIONISMO PERCUTANEO
LA VIA TRANSRADIAL DEBERIA SER EL ACCESO DE ELECCION PARA TODO PACIENTE CONSIN SCA TRATADOS CON INTERVENCIONISMO PERCUTANEO
GRACIAS POR SU ATENCION
MACE
Mortality
No interaction between access and anticoagulant use in a post- hoc analysis of the subgroup of 7213 patients randomized to bivalirudin or unfractionated heparin for the two co-primary outcomes all-cause mortality or BARC 3 or 5 bleeding
Relevance of bleeding as a clinical endpoint
bull Availability of potent antithrombotic therapy including ndash ASA ndash P2Y12 inhibitors (clopidogrel prasugrel ticagrelor) ndash heparin ndash GP IIbIIIa inhibitors ndash direct thrombin inhibitors
bull has led to a reduction in ischemic events bull but is associated with an increased risk of
bleeding bull the increase in bleeding is associated with worse
clinical outcome
Rationale for a new bleeding definition
bull Increased importance of bleeding as prognostic factor
bull Need for assessment of bleeding in RCTs and registries
bull Lack of comparability bull Need for standardized definitions to avoid
erroneous conclusions
ndash regarding safety of a given agent ndash regarding superiority of one agent over another
Open questions regarding BARC
bull Why 48-hour window for CABG-related bleeding
bull Why type 1 bdquonot actionableldquo when patient may bdquotake actionldquo such as discontinuing medication (with potentially serious consequences such as ST)
bull Why consider intraocular bleed equivalent to intracranial bleed for BARC 3c
bull Type 1 bleed subject to misinterpretation by the patient
Hicks et al (editorial) Circulation 20111232664
Conclusion
bull BARC is a new objective hierarchically graded classification of bleeding
(Mehran Circulation [June 14] 20111232736)
bull BARC is based on consensus rather than data-driven
bull Prospective validation is warranted ndash across the spectrum of IHD
ndash across management strategies (conservative invasive)
ndash in the context of all invasive procedures (PCI CABG endovascular TAVI)
Conclusion (2)
bull Final validation of BARC and proof of its utility depend on
ndash its use by all future RCTs as common safety endpoint
ndash unanimous assessment procedure (questionnaires)
bull More important than using one or the other bleeding risk score is the agreement and commitment among clinical trialists to use the same score for comparability of data
MATRIX Access
39 93 132 200 276 380 490 685 857 1002 1190
1400 1684 1972 2248
2584 2926
3256 3560
3875 4144
4452 4726
5000 5322
5655 5896 6184
6458 6742 6982 7235 7444 7638 7844 8073
8404
Cumulative enrollment by month
8404
8404
8404 patients with ACS undergoing coronary angiography plusmn PCI from 11th Oct 2011 to 7th Nov 2014
Operator Eligibility Criteria Interventional cardiologist expertise in TRI and TFI including at least 75 transradial coronary interventions and at least 50 of interventions performed via radial route in the year preceding site initiation
Complete follow-up to 30 days available in 4183 (997) of radial and 4191 (99middot6) of femoral cohorts
Am Heart J 2014 Dec168(6)838-45e6
Cross Over and Procedural Success Rates
941 of radial and 974 of femoral cohorts received respective treatment as allocated
In 58 of radial and 23 of TF cohort the allocated access was attempted but failed
In 3 (01) in the radial and 13 (03) patients in the femoral groups the allocated access was not attempted
P=077 Plt0001
TIMI lt3 andor final stenosis gt30
88
103
15 significant reduction at nominal 5 alpha
which is however NOT significant at the pre-specificed
alpha of 25
Primary EP MACE
Femoral
Radial
Rate Ratio 083 95 CI 073 to 096 p=00092
117
98
NNTB 53 Femoral
Radial
Primary EP NACE
Mortalidad Total
IAM
Fatal and ST EPs All-Cause Cardiac non-CV mortality type of stent thrombosis
RR072
(053-099)
P=0045
RR 075
(054-104)
P=008 1
13
06
1
0
02
04
06
08
1
12
14
Radial Femoral
P=069
P=066
Mortality Stent Thrombosis
NNTB 167
Bleeding endpoints BARC TIMI GUSTO access vs non-access related
14
25
P=0013
RR 067 049-092
P=00004
RR 037 021-066
BARC 3 or 5
P=00098
RR 064 045-090
P=008
RR 072 050-104 P=020
RR 078 053-114
Major
or minor
moderate
or severe
P=082
P=068
Rardial Better Femoral Better 1
HAZARD RATIO (95 CI)
P-VALUES
Superiority Interaction
089 Intermediate (548-991)
075 (060-094)
104 (082-132) 076 0011
Centrersquos annual
volume of PCI
Low (247-544)
Intermediate (654-790)
Centrersquos
Proportion of
radial PCI
Low (149-644)
NSTE-ACS (tpndash) ACS type
STEMI
lt75 Age
ge75 023 088 (070-109)
082 (068-097) 0023 062
NACE Subgroup Analysis
High (1000-1950)
High (800-980)
NSTE-ACS (tp+)
Men Sex
Women
lt25 BMI
ge25
No
Ticagrelor or
prasugrel Yes
No Diabetes
Yes
lt60 GFR
ge60
No
History of
PVD Yes
2 025 050
075 (058-097) 0025
00048
101 (079-129)
095 (075 -122) 071
095
064 (051-080) lt0001
044
086 (068-108)
058 (033-103) 0059
019
085 (071-102) 007
0012 072 (056-093)
089 (076-105) 016 018
009 086 (073-102)
079 (063-099) 0038 053
007 083 (068-102)
084 (070-101) 006 094
045 091 (071-117)
080 (068-094) 008 043
001 078 (065-094)
086 (070-107) 018 051
060 091 (064-130)
083 (071-096) 0012 064
Radial Better Femoral Better 1
HAZARD RATIO (95 CI)
P-VALUES
Superiority Interaction
Intermediate (654-790)
Centrersquos
Proportion
of radial PCI
Low (149-644)
NSTE-ACS (tpndash) ACS
type
STEMI
Subgroup Analysis
High (800-980)
NSTE-ACS (tp+)
2
00157
128 (071-232)
069 (040 -119) 018
041
048 (028-081) 0006
010
087 (059-129) 049
049 (028-087) 0012
Intermediate (654-790) Centrersquos
Proportion
of radial PCI
Low (149-644)
NSTE-ACS (tpndash) ACS
type
STEMI
High (800-980)
NSTE-ACS (tp+)
020
090 (054-150)
057 (031 -103) 006
068
056 (032-097) 0035
054
062 (041-094)
166 (028-100) 058
0022
070 (042-117) 017
Mortality
Bleeding
4 050 025
1 2 050 025
Updated Meta-analysis 19328 ACS patients being randomly allocated to radial or femoral access
Rardial Better Femoral Better 1 4 025 050 2
Pre-Rival RIVAL Post-RIVAL MATRI
X Combined
Non-CABG
major bleeds
Death
myocardial
infarction or
stroke
Death
Myocardial
Infarction
Stroke
Pre-Rival RIVAL Post-RIVAL MATRI
X Combined
Pre-Rival RIVAL Post-RIVAL MATRI
X Combined
Pre-Rival RIVAL Post-RIVAL MATRI
X Combined
Pre-Rival RIVAL Post-RIVAL MATRI
X Combined
SUBGROUP Risk Ratio (95CI) P Value
Heterogenity
P Value I2
073 (043-123) 039 (023-067)
058 (046-072)
041 (022-076)
lt00001 0 05
1
067 (048-093) 086 (076-098) 086 (077-095)
098 (076-127)
00051 0 09
7
058 (039-087) 073 (053-099) 072 (060-088) 00011 0 10
0
085 (039-190) 091 (078-106) 091 (079-104)
092 (065-131)
01
6 0 08
8
068 (049-092)
082 (052-129)
077 (046-128) 086 (058-129)
073 (012-447)
140 (045-440) 100 (050-200) 105 (069-160)
143 (072-283)
08
0 0 07
5
026 (006-123)
Summary bull Among patients with an ACS with or without ST-segment
elevation who underwent invasive management the use
of radial access for coronary angiography plusmn PCI reduced
the rate of net adverse clinical events with a number
needed to treat for benefit of 53
ndash Differences between groups were driven by reductions in BARC
major bleeding unrelated to CABG and all-cause mortality with
radial access
bull Our results in conjunction with the updated meta-
analysis suggest that radial approach should
become the default access for patients with
ACS undergoing invasive management
Radial Acces 61000 menos Muertes
LA VIA TRANSRADIAL DEBERIA SER EL ACCESO DE ELECCION o ldquo DEFAULTrdquo PARA LOS PACIENTES CON SCA TRATADOS CON INTERVENCIONISMO PERCUTANEO
LA VIA TRANSRADIAL DEBERIA SER EL ACCESO DE ELECCION PARA TODO PACIENTE CONSIN SCA TRATADOS CON INTERVENCIONISMO PERCUTANEO
GRACIAS POR SU ATENCION
MACE
Mortality
No interaction between access and anticoagulant use in a post- hoc analysis of the subgroup of 7213 patients randomized to bivalirudin or unfractionated heparin for the two co-primary outcomes all-cause mortality or BARC 3 or 5 bleeding
Relevance of bleeding as a clinical endpoint
bull Availability of potent antithrombotic therapy including ndash ASA ndash P2Y12 inhibitors (clopidogrel prasugrel ticagrelor) ndash heparin ndash GP IIbIIIa inhibitors ndash direct thrombin inhibitors
bull has led to a reduction in ischemic events bull but is associated with an increased risk of
bleeding bull the increase in bleeding is associated with worse
clinical outcome
Rationale for a new bleeding definition
bull Increased importance of bleeding as prognostic factor
bull Need for assessment of bleeding in RCTs and registries
bull Lack of comparability bull Need for standardized definitions to avoid
erroneous conclusions
ndash regarding safety of a given agent ndash regarding superiority of one agent over another
Open questions regarding BARC
bull Why 48-hour window for CABG-related bleeding
bull Why type 1 bdquonot actionableldquo when patient may bdquotake actionldquo such as discontinuing medication (with potentially serious consequences such as ST)
bull Why consider intraocular bleed equivalent to intracranial bleed for BARC 3c
bull Type 1 bleed subject to misinterpretation by the patient
Hicks et al (editorial) Circulation 20111232664
Conclusion
bull BARC is a new objective hierarchically graded classification of bleeding
(Mehran Circulation [June 14] 20111232736)
bull BARC is based on consensus rather than data-driven
bull Prospective validation is warranted ndash across the spectrum of IHD
ndash across management strategies (conservative invasive)
ndash in the context of all invasive procedures (PCI CABG endovascular TAVI)
Conclusion (2)
bull Final validation of BARC and proof of its utility depend on
ndash its use by all future RCTs as common safety endpoint
ndash unanimous assessment procedure (questionnaires)
bull More important than using one or the other bleeding risk score is the agreement and commitment among clinical trialists to use the same score for comparability of data
Cross Over and Procedural Success Rates
941 of radial and 974 of femoral cohorts received respective treatment as allocated
In 58 of radial and 23 of TF cohort the allocated access was attempted but failed
In 3 (01) in the radial and 13 (03) patients in the femoral groups the allocated access was not attempted
P=077 Plt0001
TIMI lt3 andor final stenosis gt30
88
103
15 significant reduction at nominal 5 alpha
which is however NOT significant at the pre-specificed
alpha of 25
Primary EP MACE
Femoral
Radial
Rate Ratio 083 95 CI 073 to 096 p=00092
117
98
NNTB 53 Femoral
Radial
Primary EP NACE
Mortalidad Total
IAM
Fatal and ST EPs All-Cause Cardiac non-CV mortality type of stent thrombosis
RR072
(053-099)
P=0045
RR 075
(054-104)
P=008 1
13
06
1
0
02
04
06
08
1
12
14
Radial Femoral
P=069
P=066
Mortality Stent Thrombosis
NNTB 167
Bleeding endpoints BARC TIMI GUSTO access vs non-access related
14
25
P=0013
RR 067 049-092
P=00004
RR 037 021-066
BARC 3 or 5
P=00098
RR 064 045-090
P=008
RR 072 050-104 P=020
RR 078 053-114
Major
or minor
moderate
or severe
P=082
P=068
Rardial Better Femoral Better 1
HAZARD RATIO (95 CI)
P-VALUES
Superiority Interaction
089 Intermediate (548-991)
075 (060-094)
104 (082-132) 076 0011
Centrersquos annual
volume of PCI
Low (247-544)
Intermediate (654-790)
Centrersquos
Proportion of
radial PCI
Low (149-644)
NSTE-ACS (tpndash) ACS type
STEMI
lt75 Age
ge75 023 088 (070-109)
082 (068-097) 0023 062
NACE Subgroup Analysis
High (1000-1950)
High (800-980)
NSTE-ACS (tp+)
Men Sex
Women
lt25 BMI
ge25
No
Ticagrelor or
prasugrel Yes
No Diabetes
Yes
lt60 GFR
ge60
No
History of
PVD Yes
2 025 050
075 (058-097) 0025
00048
101 (079-129)
095 (075 -122) 071
095
064 (051-080) lt0001
044
086 (068-108)
058 (033-103) 0059
019
085 (071-102) 007
0012 072 (056-093)
089 (076-105) 016 018
009 086 (073-102)
079 (063-099) 0038 053
007 083 (068-102)
084 (070-101) 006 094
045 091 (071-117)
080 (068-094) 008 043
001 078 (065-094)
086 (070-107) 018 051
060 091 (064-130)
083 (071-096) 0012 064
Radial Better Femoral Better 1
HAZARD RATIO (95 CI)
P-VALUES
Superiority Interaction
Intermediate (654-790)
Centrersquos
Proportion
of radial PCI
Low (149-644)
NSTE-ACS (tpndash) ACS
type
STEMI
Subgroup Analysis
High (800-980)
NSTE-ACS (tp+)
2
00157
128 (071-232)
069 (040 -119) 018
041
048 (028-081) 0006
010
087 (059-129) 049
049 (028-087) 0012
Intermediate (654-790) Centrersquos
Proportion
of radial PCI
Low (149-644)
NSTE-ACS (tpndash) ACS
type
STEMI
High (800-980)
NSTE-ACS (tp+)
020
090 (054-150)
057 (031 -103) 006
068
056 (032-097) 0035
054
062 (041-094)
166 (028-100) 058
0022
070 (042-117) 017
Mortality
Bleeding
4 050 025
1 2 050 025
Updated Meta-analysis 19328 ACS patients being randomly allocated to radial or femoral access
Rardial Better Femoral Better 1 4 025 050 2
Pre-Rival RIVAL Post-RIVAL MATRI
X Combined
Non-CABG
major bleeds
Death
myocardial
infarction or
stroke
Death
Myocardial
Infarction
Stroke
Pre-Rival RIVAL Post-RIVAL MATRI
X Combined
Pre-Rival RIVAL Post-RIVAL MATRI
X Combined
Pre-Rival RIVAL Post-RIVAL MATRI
X Combined
Pre-Rival RIVAL Post-RIVAL MATRI
X Combined
SUBGROUP Risk Ratio (95CI) P Value
Heterogenity
P Value I2
073 (043-123) 039 (023-067)
058 (046-072)
041 (022-076)
lt00001 0 05
1
067 (048-093) 086 (076-098) 086 (077-095)
098 (076-127)
00051 0 09
7
058 (039-087) 073 (053-099) 072 (060-088) 00011 0 10
0
085 (039-190) 091 (078-106) 091 (079-104)
092 (065-131)
01
6 0 08
8
068 (049-092)
082 (052-129)
077 (046-128) 086 (058-129)
073 (012-447)
140 (045-440) 100 (050-200) 105 (069-160)
143 (072-283)
08
0 0 07
5
026 (006-123)
Summary bull Among patients with an ACS with or without ST-segment
elevation who underwent invasive management the use
of radial access for coronary angiography plusmn PCI reduced
the rate of net adverse clinical events with a number
needed to treat for benefit of 53
ndash Differences between groups were driven by reductions in BARC
major bleeding unrelated to CABG and all-cause mortality with
radial access
bull Our results in conjunction with the updated meta-
analysis suggest that radial approach should
become the default access for patients with
ACS undergoing invasive management
Radial Acces 61000 menos Muertes
LA VIA TRANSRADIAL DEBERIA SER EL ACCESO DE ELECCION o ldquo DEFAULTrdquo PARA LOS PACIENTES CON SCA TRATADOS CON INTERVENCIONISMO PERCUTANEO
LA VIA TRANSRADIAL DEBERIA SER EL ACCESO DE ELECCION PARA TODO PACIENTE CONSIN SCA TRATADOS CON INTERVENCIONISMO PERCUTANEO
GRACIAS POR SU ATENCION
MACE
Mortality
No interaction between access and anticoagulant use in a post- hoc analysis of the subgroup of 7213 patients randomized to bivalirudin or unfractionated heparin for the two co-primary outcomes all-cause mortality or BARC 3 or 5 bleeding
Relevance of bleeding as a clinical endpoint
bull Availability of potent antithrombotic therapy including ndash ASA ndash P2Y12 inhibitors (clopidogrel prasugrel ticagrelor) ndash heparin ndash GP IIbIIIa inhibitors ndash direct thrombin inhibitors
bull has led to a reduction in ischemic events bull but is associated with an increased risk of
bleeding bull the increase in bleeding is associated with worse
clinical outcome
Rationale for a new bleeding definition
bull Increased importance of bleeding as prognostic factor
bull Need for assessment of bleeding in RCTs and registries
bull Lack of comparability bull Need for standardized definitions to avoid
erroneous conclusions
ndash regarding safety of a given agent ndash regarding superiority of one agent over another
Open questions regarding BARC
bull Why 48-hour window for CABG-related bleeding
bull Why type 1 bdquonot actionableldquo when patient may bdquotake actionldquo such as discontinuing medication (with potentially serious consequences such as ST)
bull Why consider intraocular bleed equivalent to intracranial bleed for BARC 3c
bull Type 1 bleed subject to misinterpretation by the patient
Hicks et al (editorial) Circulation 20111232664
Conclusion
bull BARC is a new objective hierarchically graded classification of bleeding
(Mehran Circulation [June 14] 20111232736)
bull BARC is based on consensus rather than data-driven
bull Prospective validation is warranted ndash across the spectrum of IHD
ndash across management strategies (conservative invasive)
ndash in the context of all invasive procedures (PCI CABG endovascular TAVI)
Conclusion (2)
bull Final validation of BARC and proof of its utility depend on
ndash its use by all future RCTs as common safety endpoint
ndash unanimous assessment procedure (questionnaires)
bull More important than using one or the other bleeding risk score is the agreement and commitment among clinical trialists to use the same score for comparability of data
88
103
15 significant reduction at nominal 5 alpha
which is however NOT significant at the pre-specificed
alpha of 25
Primary EP MACE
Femoral
Radial
Rate Ratio 083 95 CI 073 to 096 p=00092
117
98
NNTB 53 Femoral
Radial
Primary EP NACE
Mortalidad Total
IAM
Fatal and ST EPs All-Cause Cardiac non-CV mortality type of stent thrombosis
RR072
(053-099)
P=0045
RR 075
(054-104)
P=008 1
13
06
1
0
02
04
06
08
1
12
14
Radial Femoral
P=069
P=066
Mortality Stent Thrombosis
NNTB 167
Bleeding endpoints BARC TIMI GUSTO access vs non-access related
14
25
P=0013
RR 067 049-092
P=00004
RR 037 021-066
BARC 3 or 5
P=00098
RR 064 045-090
P=008
RR 072 050-104 P=020
RR 078 053-114
Major
or minor
moderate
or severe
P=082
P=068
Rardial Better Femoral Better 1
HAZARD RATIO (95 CI)
P-VALUES
Superiority Interaction
089 Intermediate (548-991)
075 (060-094)
104 (082-132) 076 0011
Centrersquos annual
volume of PCI
Low (247-544)
Intermediate (654-790)
Centrersquos
Proportion of
radial PCI
Low (149-644)
NSTE-ACS (tpndash) ACS type
STEMI
lt75 Age
ge75 023 088 (070-109)
082 (068-097) 0023 062
NACE Subgroup Analysis
High (1000-1950)
High (800-980)
NSTE-ACS (tp+)
Men Sex
Women
lt25 BMI
ge25
No
Ticagrelor or
prasugrel Yes
No Diabetes
Yes
lt60 GFR
ge60
No
History of
PVD Yes
2 025 050
075 (058-097) 0025
00048
101 (079-129)
095 (075 -122) 071
095
064 (051-080) lt0001
044
086 (068-108)
058 (033-103) 0059
019
085 (071-102) 007
0012 072 (056-093)
089 (076-105) 016 018
009 086 (073-102)
079 (063-099) 0038 053
007 083 (068-102)
084 (070-101) 006 094
045 091 (071-117)
080 (068-094) 008 043
001 078 (065-094)
086 (070-107) 018 051
060 091 (064-130)
083 (071-096) 0012 064
Radial Better Femoral Better 1
HAZARD RATIO (95 CI)
P-VALUES
Superiority Interaction
Intermediate (654-790)
Centrersquos
Proportion
of radial PCI
Low (149-644)
NSTE-ACS (tpndash) ACS
type
STEMI
Subgroup Analysis
High (800-980)
NSTE-ACS (tp+)
2
00157
128 (071-232)
069 (040 -119) 018
041
048 (028-081) 0006
010
087 (059-129) 049
049 (028-087) 0012
Intermediate (654-790) Centrersquos
Proportion
of radial PCI
Low (149-644)
NSTE-ACS (tpndash) ACS
type
STEMI
High (800-980)
NSTE-ACS (tp+)
020
090 (054-150)
057 (031 -103) 006
068
056 (032-097) 0035
054
062 (041-094)
166 (028-100) 058
0022
070 (042-117) 017
Mortality
Bleeding
4 050 025
1 2 050 025
Updated Meta-analysis 19328 ACS patients being randomly allocated to radial or femoral access
Rardial Better Femoral Better 1 4 025 050 2
Pre-Rival RIVAL Post-RIVAL MATRI
X Combined
Non-CABG
major bleeds
Death
myocardial
infarction or
stroke
Death
Myocardial
Infarction
Stroke
Pre-Rival RIVAL Post-RIVAL MATRI
X Combined
Pre-Rival RIVAL Post-RIVAL MATRI
X Combined
Pre-Rival RIVAL Post-RIVAL MATRI
X Combined
Pre-Rival RIVAL Post-RIVAL MATRI
X Combined
SUBGROUP Risk Ratio (95CI) P Value
Heterogenity
P Value I2
073 (043-123) 039 (023-067)
058 (046-072)
041 (022-076)
lt00001 0 05
1
067 (048-093) 086 (076-098) 086 (077-095)
098 (076-127)
00051 0 09
7
058 (039-087) 073 (053-099) 072 (060-088) 00011 0 10
0
085 (039-190) 091 (078-106) 091 (079-104)
092 (065-131)
01
6 0 08
8
068 (049-092)
082 (052-129)
077 (046-128) 086 (058-129)
073 (012-447)
140 (045-440) 100 (050-200) 105 (069-160)
143 (072-283)
08
0 0 07
5
026 (006-123)
Summary bull Among patients with an ACS with or without ST-segment
elevation who underwent invasive management the use
of radial access for coronary angiography plusmn PCI reduced
the rate of net adverse clinical events with a number
needed to treat for benefit of 53
ndash Differences between groups were driven by reductions in BARC
major bleeding unrelated to CABG and all-cause mortality with
radial access
bull Our results in conjunction with the updated meta-
analysis suggest that radial approach should
become the default access for patients with
ACS undergoing invasive management
Radial Acces 61000 menos Muertes
LA VIA TRANSRADIAL DEBERIA SER EL ACCESO DE ELECCION o ldquo DEFAULTrdquo PARA LOS PACIENTES CON SCA TRATADOS CON INTERVENCIONISMO PERCUTANEO
LA VIA TRANSRADIAL DEBERIA SER EL ACCESO DE ELECCION PARA TODO PACIENTE CONSIN SCA TRATADOS CON INTERVENCIONISMO PERCUTANEO
GRACIAS POR SU ATENCION
MACE
Mortality
No interaction between access and anticoagulant use in a post- hoc analysis of the subgroup of 7213 patients randomized to bivalirudin or unfractionated heparin for the two co-primary outcomes all-cause mortality or BARC 3 or 5 bleeding
Relevance of bleeding as a clinical endpoint
bull Availability of potent antithrombotic therapy including ndash ASA ndash P2Y12 inhibitors (clopidogrel prasugrel ticagrelor) ndash heparin ndash GP IIbIIIa inhibitors ndash direct thrombin inhibitors
bull has led to a reduction in ischemic events bull but is associated with an increased risk of
bleeding bull the increase in bleeding is associated with worse
clinical outcome
Rationale for a new bleeding definition
bull Increased importance of bleeding as prognostic factor
bull Need for assessment of bleeding in RCTs and registries
bull Lack of comparability bull Need for standardized definitions to avoid
erroneous conclusions
ndash regarding safety of a given agent ndash regarding superiority of one agent over another
Open questions regarding BARC
bull Why 48-hour window for CABG-related bleeding
bull Why type 1 bdquonot actionableldquo when patient may bdquotake actionldquo such as discontinuing medication (with potentially serious consequences such as ST)
bull Why consider intraocular bleed equivalent to intracranial bleed for BARC 3c
bull Type 1 bleed subject to misinterpretation by the patient
Hicks et al (editorial) Circulation 20111232664
Conclusion
bull BARC is a new objective hierarchically graded classification of bleeding
(Mehran Circulation [June 14] 20111232736)
bull BARC is based on consensus rather than data-driven
bull Prospective validation is warranted ndash across the spectrum of IHD
ndash across management strategies (conservative invasive)
ndash in the context of all invasive procedures (PCI CABG endovascular TAVI)
Conclusion (2)
bull Final validation of BARC and proof of its utility depend on
ndash its use by all future RCTs as common safety endpoint
ndash unanimous assessment procedure (questionnaires)
bull More important than using one or the other bleeding risk score is the agreement and commitment among clinical trialists to use the same score for comparability of data
Rate Ratio 083 95 CI 073 to 096 p=00092
117
98
NNTB 53 Femoral
Radial
Primary EP NACE
Mortalidad Total
IAM
Fatal and ST EPs All-Cause Cardiac non-CV mortality type of stent thrombosis
RR072
(053-099)
P=0045
RR 075
(054-104)
P=008 1
13
06
1
0
02
04
06
08
1
12
14
Radial Femoral
P=069
P=066
Mortality Stent Thrombosis
NNTB 167
Bleeding endpoints BARC TIMI GUSTO access vs non-access related
14
25
P=0013
RR 067 049-092
P=00004
RR 037 021-066
BARC 3 or 5
P=00098
RR 064 045-090
P=008
RR 072 050-104 P=020
RR 078 053-114
Major
or minor
moderate
or severe
P=082
P=068
Rardial Better Femoral Better 1
HAZARD RATIO (95 CI)
P-VALUES
Superiority Interaction
089 Intermediate (548-991)
075 (060-094)
104 (082-132) 076 0011
Centrersquos annual
volume of PCI
Low (247-544)
Intermediate (654-790)
Centrersquos
Proportion of
radial PCI
Low (149-644)
NSTE-ACS (tpndash) ACS type
STEMI
lt75 Age
ge75 023 088 (070-109)
082 (068-097) 0023 062
NACE Subgroup Analysis
High (1000-1950)
High (800-980)
NSTE-ACS (tp+)
Men Sex
Women
lt25 BMI
ge25
No
Ticagrelor or
prasugrel Yes
No Diabetes
Yes
lt60 GFR
ge60
No
History of
PVD Yes
2 025 050
075 (058-097) 0025
00048
101 (079-129)
095 (075 -122) 071
095
064 (051-080) lt0001
044
086 (068-108)
058 (033-103) 0059
019
085 (071-102) 007
0012 072 (056-093)
089 (076-105) 016 018
009 086 (073-102)
079 (063-099) 0038 053
007 083 (068-102)
084 (070-101) 006 094
045 091 (071-117)
080 (068-094) 008 043
001 078 (065-094)
086 (070-107) 018 051
060 091 (064-130)
083 (071-096) 0012 064
Radial Better Femoral Better 1
HAZARD RATIO (95 CI)
P-VALUES
Superiority Interaction
Intermediate (654-790)
Centrersquos
Proportion
of radial PCI
Low (149-644)
NSTE-ACS (tpndash) ACS
type
STEMI
Subgroup Analysis
High (800-980)
NSTE-ACS (tp+)
2
00157
128 (071-232)
069 (040 -119) 018
041
048 (028-081) 0006
010
087 (059-129) 049
049 (028-087) 0012
Intermediate (654-790) Centrersquos
Proportion
of radial PCI
Low (149-644)
NSTE-ACS (tpndash) ACS
type
STEMI
High (800-980)
NSTE-ACS (tp+)
020
090 (054-150)
057 (031 -103) 006
068
056 (032-097) 0035
054
062 (041-094)
166 (028-100) 058
0022
070 (042-117) 017
Mortality
Bleeding
4 050 025
1 2 050 025
Updated Meta-analysis 19328 ACS patients being randomly allocated to radial or femoral access
Rardial Better Femoral Better 1 4 025 050 2
Pre-Rival RIVAL Post-RIVAL MATRI
X Combined
Non-CABG
major bleeds
Death
myocardial
infarction or
stroke
Death
Myocardial
Infarction
Stroke
Pre-Rival RIVAL Post-RIVAL MATRI
X Combined
Pre-Rival RIVAL Post-RIVAL MATRI
X Combined
Pre-Rival RIVAL Post-RIVAL MATRI
X Combined
Pre-Rival RIVAL Post-RIVAL MATRI
X Combined
SUBGROUP Risk Ratio (95CI) P Value
Heterogenity
P Value I2
073 (043-123) 039 (023-067)
058 (046-072)
041 (022-076)
lt00001 0 05
1
067 (048-093) 086 (076-098) 086 (077-095)
098 (076-127)
00051 0 09
7
058 (039-087) 073 (053-099) 072 (060-088) 00011 0 10
0
085 (039-190) 091 (078-106) 091 (079-104)
092 (065-131)
01
6 0 08
8
068 (049-092)
082 (052-129)
077 (046-128) 086 (058-129)
073 (012-447)
140 (045-440) 100 (050-200) 105 (069-160)
143 (072-283)
08
0 0 07
5
026 (006-123)
Summary bull Among patients with an ACS with or without ST-segment
elevation who underwent invasive management the use
of radial access for coronary angiography plusmn PCI reduced
the rate of net adverse clinical events with a number
needed to treat for benefit of 53
ndash Differences between groups were driven by reductions in BARC
major bleeding unrelated to CABG and all-cause mortality with
radial access
bull Our results in conjunction with the updated meta-
analysis suggest that radial approach should
become the default access for patients with
ACS undergoing invasive management
Radial Acces 61000 menos Muertes
LA VIA TRANSRADIAL DEBERIA SER EL ACCESO DE ELECCION o ldquo DEFAULTrdquo PARA LOS PACIENTES CON SCA TRATADOS CON INTERVENCIONISMO PERCUTANEO
LA VIA TRANSRADIAL DEBERIA SER EL ACCESO DE ELECCION PARA TODO PACIENTE CONSIN SCA TRATADOS CON INTERVENCIONISMO PERCUTANEO
GRACIAS POR SU ATENCION
MACE
Mortality
No interaction between access and anticoagulant use in a post- hoc analysis of the subgroup of 7213 patients randomized to bivalirudin or unfractionated heparin for the two co-primary outcomes all-cause mortality or BARC 3 or 5 bleeding
Relevance of bleeding as a clinical endpoint
bull Availability of potent antithrombotic therapy including ndash ASA ndash P2Y12 inhibitors (clopidogrel prasugrel ticagrelor) ndash heparin ndash GP IIbIIIa inhibitors ndash direct thrombin inhibitors
bull has led to a reduction in ischemic events bull but is associated with an increased risk of
bleeding bull the increase in bleeding is associated with worse
clinical outcome
Rationale for a new bleeding definition
bull Increased importance of bleeding as prognostic factor
bull Need for assessment of bleeding in RCTs and registries
bull Lack of comparability bull Need for standardized definitions to avoid
erroneous conclusions
ndash regarding safety of a given agent ndash regarding superiority of one agent over another
Open questions regarding BARC
bull Why 48-hour window for CABG-related bleeding
bull Why type 1 bdquonot actionableldquo when patient may bdquotake actionldquo such as discontinuing medication (with potentially serious consequences such as ST)
bull Why consider intraocular bleed equivalent to intracranial bleed for BARC 3c
bull Type 1 bleed subject to misinterpretation by the patient
Hicks et al (editorial) Circulation 20111232664
Conclusion
bull BARC is a new objective hierarchically graded classification of bleeding
(Mehran Circulation [June 14] 20111232736)
bull BARC is based on consensus rather than data-driven
bull Prospective validation is warranted ndash across the spectrum of IHD
ndash across management strategies (conservative invasive)
ndash in the context of all invasive procedures (PCI CABG endovascular TAVI)
Conclusion (2)
bull Final validation of BARC and proof of its utility depend on
ndash its use by all future RCTs as common safety endpoint
ndash unanimous assessment procedure (questionnaires)
bull More important than using one or the other bleeding risk score is the agreement and commitment among clinical trialists to use the same score for comparability of data
Mortalidad Total
IAM
Fatal and ST EPs All-Cause Cardiac non-CV mortality type of stent thrombosis
RR072
(053-099)
P=0045
RR 075
(054-104)
P=008 1
13
06
1
0
02
04
06
08
1
12
14
Radial Femoral
P=069
P=066
Mortality Stent Thrombosis
NNTB 167
Bleeding endpoints BARC TIMI GUSTO access vs non-access related
14
25
P=0013
RR 067 049-092
P=00004
RR 037 021-066
BARC 3 or 5
P=00098
RR 064 045-090
P=008
RR 072 050-104 P=020
RR 078 053-114
Major
or minor
moderate
or severe
P=082
P=068
Rardial Better Femoral Better 1
HAZARD RATIO (95 CI)
P-VALUES
Superiority Interaction
089 Intermediate (548-991)
075 (060-094)
104 (082-132) 076 0011
Centrersquos annual
volume of PCI
Low (247-544)
Intermediate (654-790)
Centrersquos
Proportion of
radial PCI
Low (149-644)
NSTE-ACS (tpndash) ACS type
STEMI
lt75 Age
ge75 023 088 (070-109)
082 (068-097) 0023 062
NACE Subgroup Analysis
High (1000-1950)
High (800-980)
NSTE-ACS (tp+)
Men Sex
Women
lt25 BMI
ge25
No
Ticagrelor or
prasugrel Yes
No Diabetes
Yes
lt60 GFR
ge60
No
History of
PVD Yes
2 025 050
075 (058-097) 0025
00048
101 (079-129)
095 (075 -122) 071
095
064 (051-080) lt0001
044
086 (068-108)
058 (033-103) 0059
019
085 (071-102) 007
0012 072 (056-093)
089 (076-105) 016 018
009 086 (073-102)
079 (063-099) 0038 053
007 083 (068-102)
084 (070-101) 006 094
045 091 (071-117)
080 (068-094) 008 043
001 078 (065-094)
086 (070-107) 018 051
060 091 (064-130)
083 (071-096) 0012 064
Radial Better Femoral Better 1
HAZARD RATIO (95 CI)
P-VALUES
Superiority Interaction
Intermediate (654-790)
Centrersquos
Proportion
of radial PCI
Low (149-644)
NSTE-ACS (tpndash) ACS
type
STEMI
Subgroup Analysis
High (800-980)
NSTE-ACS (tp+)
2
00157
128 (071-232)
069 (040 -119) 018
041
048 (028-081) 0006
010
087 (059-129) 049
049 (028-087) 0012
Intermediate (654-790) Centrersquos
Proportion
of radial PCI
Low (149-644)
NSTE-ACS (tpndash) ACS
type
STEMI
High (800-980)
NSTE-ACS (tp+)
020
090 (054-150)
057 (031 -103) 006
068
056 (032-097) 0035
054
062 (041-094)
166 (028-100) 058
0022
070 (042-117) 017
Mortality
Bleeding
4 050 025
1 2 050 025
Updated Meta-analysis 19328 ACS patients being randomly allocated to radial or femoral access
Rardial Better Femoral Better 1 4 025 050 2
Pre-Rival RIVAL Post-RIVAL MATRI
X Combined
Non-CABG
major bleeds
Death
myocardial
infarction or
stroke
Death
Myocardial
Infarction
Stroke
Pre-Rival RIVAL Post-RIVAL MATRI
X Combined
Pre-Rival RIVAL Post-RIVAL MATRI
X Combined
Pre-Rival RIVAL Post-RIVAL MATRI
X Combined
Pre-Rival RIVAL Post-RIVAL MATRI
X Combined
SUBGROUP Risk Ratio (95CI) P Value
Heterogenity
P Value I2
073 (043-123) 039 (023-067)
058 (046-072)
041 (022-076)
lt00001 0 05
1
067 (048-093) 086 (076-098) 086 (077-095)
098 (076-127)
00051 0 09
7
058 (039-087) 073 (053-099) 072 (060-088) 00011 0 10
0
085 (039-190) 091 (078-106) 091 (079-104)
092 (065-131)
01
6 0 08
8
068 (049-092)
082 (052-129)
077 (046-128) 086 (058-129)
073 (012-447)
140 (045-440) 100 (050-200) 105 (069-160)
143 (072-283)
08
0 0 07
5
026 (006-123)
Summary bull Among patients with an ACS with or without ST-segment
elevation who underwent invasive management the use
of radial access for coronary angiography plusmn PCI reduced
the rate of net adverse clinical events with a number
needed to treat for benefit of 53
ndash Differences between groups were driven by reductions in BARC
major bleeding unrelated to CABG and all-cause mortality with
radial access
bull Our results in conjunction with the updated meta-
analysis suggest that radial approach should
become the default access for patients with
ACS undergoing invasive management
Radial Acces 61000 menos Muertes
LA VIA TRANSRADIAL DEBERIA SER EL ACCESO DE ELECCION o ldquo DEFAULTrdquo PARA LOS PACIENTES CON SCA TRATADOS CON INTERVENCIONISMO PERCUTANEO
LA VIA TRANSRADIAL DEBERIA SER EL ACCESO DE ELECCION PARA TODO PACIENTE CONSIN SCA TRATADOS CON INTERVENCIONISMO PERCUTANEO
GRACIAS POR SU ATENCION
MACE
Mortality
No interaction between access and anticoagulant use in a post- hoc analysis of the subgroup of 7213 patients randomized to bivalirudin or unfractionated heparin for the two co-primary outcomes all-cause mortality or BARC 3 or 5 bleeding
Relevance of bleeding as a clinical endpoint
bull Availability of potent antithrombotic therapy including ndash ASA ndash P2Y12 inhibitors (clopidogrel prasugrel ticagrelor) ndash heparin ndash GP IIbIIIa inhibitors ndash direct thrombin inhibitors
bull has led to a reduction in ischemic events bull but is associated with an increased risk of
bleeding bull the increase in bleeding is associated with worse
clinical outcome
Rationale for a new bleeding definition
bull Increased importance of bleeding as prognostic factor
bull Need for assessment of bleeding in RCTs and registries
bull Lack of comparability bull Need for standardized definitions to avoid
erroneous conclusions
ndash regarding safety of a given agent ndash regarding superiority of one agent over another
Open questions regarding BARC
bull Why 48-hour window for CABG-related bleeding
bull Why type 1 bdquonot actionableldquo when patient may bdquotake actionldquo such as discontinuing medication (with potentially serious consequences such as ST)
bull Why consider intraocular bleed equivalent to intracranial bleed for BARC 3c
bull Type 1 bleed subject to misinterpretation by the patient
Hicks et al (editorial) Circulation 20111232664
Conclusion
bull BARC is a new objective hierarchically graded classification of bleeding
(Mehran Circulation [June 14] 20111232736)
bull BARC is based on consensus rather than data-driven
bull Prospective validation is warranted ndash across the spectrum of IHD
ndash across management strategies (conservative invasive)
ndash in the context of all invasive procedures (PCI CABG endovascular TAVI)
Conclusion (2)
bull Final validation of BARC and proof of its utility depend on
ndash its use by all future RCTs as common safety endpoint
ndash unanimous assessment procedure (questionnaires)
bull More important than using one or the other bleeding risk score is the agreement and commitment among clinical trialists to use the same score for comparability of data
Fatal and ST EPs All-Cause Cardiac non-CV mortality type of stent thrombosis
RR072
(053-099)
P=0045
RR 075
(054-104)
P=008 1
13
06
1
0
02
04
06
08
1
12
14
Radial Femoral
P=069
P=066
Mortality Stent Thrombosis
NNTB 167
Bleeding endpoints BARC TIMI GUSTO access vs non-access related
14
25
P=0013
RR 067 049-092
P=00004
RR 037 021-066
BARC 3 or 5
P=00098
RR 064 045-090
P=008
RR 072 050-104 P=020
RR 078 053-114
Major
or minor
moderate
or severe
P=082
P=068
Rardial Better Femoral Better 1
HAZARD RATIO (95 CI)
P-VALUES
Superiority Interaction
089 Intermediate (548-991)
075 (060-094)
104 (082-132) 076 0011
Centrersquos annual
volume of PCI
Low (247-544)
Intermediate (654-790)
Centrersquos
Proportion of
radial PCI
Low (149-644)
NSTE-ACS (tpndash) ACS type
STEMI
lt75 Age
ge75 023 088 (070-109)
082 (068-097) 0023 062
NACE Subgroup Analysis
High (1000-1950)
High (800-980)
NSTE-ACS (tp+)
Men Sex
Women
lt25 BMI
ge25
No
Ticagrelor or
prasugrel Yes
No Diabetes
Yes
lt60 GFR
ge60
No
History of
PVD Yes
2 025 050
075 (058-097) 0025
00048
101 (079-129)
095 (075 -122) 071
095
064 (051-080) lt0001
044
086 (068-108)
058 (033-103) 0059
019
085 (071-102) 007
0012 072 (056-093)
089 (076-105) 016 018
009 086 (073-102)
079 (063-099) 0038 053
007 083 (068-102)
084 (070-101) 006 094
045 091 (071-117)
080 (068-094) 008 043
001 078 (065-094)
086 (070-107) 018 051
060 091 (064-130)
083 (071-096) 0012 064
Radial Better Femoral Better 1
HAZARD RATIO (95 CI)
P-VALUES
Superiority Interaction
Intermediate (654-790)
Centrersquos
Proportion
of radial PCI
Low (149-644)
NSTE-ACS (tpndash) ACS
type
STEMI
Subgroup Analysis
High (800-980)
NSTE-ACS (tp+)
2
00157
128 (071-232)
069 (040 -119) 018
041
048 (028-081) 0006
010
087 (059-129) 049
049 (028-087) 0012
Intermediate (654-790) Centrersquos
Proportion
of radial PCI
Low (149-644)
NSTE-ACS (tpndash) ACS
type
STEMI
High (800-980)
NSTE-ACS (tp+)
020
090 (054-150)
057 (031 -103) 006
068
056 (032-097) 0035
054
062 (041-094)
166 (028-100) 058
0022
070 (042-117) 017
Mortality
Bleeding
4 050 025
1 2 050 025
Updated Meta-analysis 19328 ACS patients being randomly allocated to radial or femoral access
Rardial Better Femoral Better 1 4 025 050 2
Pre-Rival RIVAL Post-RIVAL MATRI
X Combined
Non-CABG
major bleeds
Death
myocardial
infarction or
stroke
Death
Myocardial
Infarction
Stroke
Pre-Rival RIVAL Post-RIVAL MATRI
X Combined
Pre-Rival RIVAL Post-RIVAL MATRI
X Combined
Pre-Rival RIVAL Post-RIVAL MATRI
X Combined
Pre-Rival RIVAL Post-RIVAL MATRI
X Combined
SUBGROUP Risk Ratio (95CI) P Value
Heterogenity
P Value I2
073 (043-123) 039 (023-067)
058 (046-072)
041 (022-076)
lt00001 0 05
1
067 (048-093) 086 (076-098) 086 (077-095)
098 (076-127)
00051 0 09
7
058 (039-087) 073 (053-099) 072 (060-088) 00011 0 10
0
085 (039-190) 091 (078-106) 091 (079-104)
092 (065-131)
01
6 0 08
8
068 (049-092)
082 (052-129)
077 (046-128) 086 (058-129)
073 (012-447)
140 (045-440) 100 (050-200) 105 (069-160)
143 (072-283)
08
0 0 07
5
026 (006-123)
Summary bull Among patients with an ACS with or without ST-segment
elevation who underwent invasive management the use
of radial access for coronary angiography plusmn PCI reduced
the rate of net adverse clinical events with a number
needed to treat for benefit of 53
ndash Differences between groups were driven by reductions in BARC
major bleeding unrelated to CABG and all-cause mortality with
radial access
bull Our results in conjunction with the updated meta-
analysis suggest that radial approach should
become the default access for patients with
ACS undergoing invasive management
Radial Acces 61000 menos Muertes
LA VIA TRANSRADIAL DEBERIA SER EL ACCESO DE ELECCION o ldquo DEFAULTrdquo PARA LOS PACIENTES CON SCA TRATADOS CON INTERVENCIONISMO PERCUTANEO
LA VIA TRANSRADIAL DEBERIA SER EL ACCESO DE ELECCION PARA TODO PACIENTE CONSIN SCA TRATADOS CON INTERVENCIONISMO PERCUTANEO
GRACIAS POR SU ATENCION
MACE
Mortality
No interaction between access and anticoagulant use in a post- hoc analysis of the subgroup of 7213 patients randomized to bivalirudin or unfractionated heparin for the two co-primary outcomes all-cause mortality or BARC 3 or 5 bleeding
Relevance of bleeding as a clinical endpoint
bull Availability of potent antithrombotic therapy including ndash ASA ndash P2Y12 inhibitors (clopidogrel prasugrel ticagrelor) ndash heparin ndash GP IIbIIIa inhibitors ndash direct thrombin inhibitors
bull has led to a reduction in ischemic events bull but is associated with an increased risk of
bleeding bull the increase in bleeding is associated with worse
clinical outcome
Rationale for a new bleeding definition
bull Increased importance of bleeding as prognostic factor
bull Need for assessment of bleeding in RCTs and registries
bull Lack of comparability bull Need for standardized definitions to avoid
erroneous conclusions
ndash regarding safety of a given agent ndash regarding superiority of one agent over another
Open questions regarding BARC
bull Why 48-hour window for CABG-related bleeding
bull Why type 1 bdquonot actionableldquo when patient may bdquotake actionldquo such as discontinuing medication (with potentially serious consequences such as ST)
bull Why consider intraocular bleed equivalent to intracranial bleed for BARC 3c
bull Type 1 bleed subject to misinterpretation by the patient
Hicks et al (editorial) Circulation 20111232664
Conclusion
bull BARC is a new objective hierarchically graded classification of bleeding
(Mehran Circulation [June 14] 20111232736)
bull BARC is based on consensus rather than data-driven
bull Prospective validation is warranted ndash across the spectrum of IHD
ndash across management strategies (conservative invasive)
ndash in the context of all invasive procedures (PCI CABG endovascular TAVI)
Conclusion (2)
bull Final validation of BARC and proof of its utility depend on
ndash its use by all future RCTs as common safety endpoint
ndash unanimous assessment procedure (questionnaires)
bull More important than using one or the other bleeding risk score is the agreement and commitment among clinical trialists to use the same score for comparability of data
Bleeding endpoints BARC TIMI GUSTO access vs non-access related
14
25
P=0013
RR 067 049-092
P=00004
RR 037 021-066
BARC 3 or 5
P=00098
RR 064 045-090
P=008
RR 072 050-104 P=020
RR 078 053-114
Major
or minor
moderate
or severe
P=082
P=068
Rardial Better Femoral Better 1
HAZARD RATIO (95 CI)
P-VALUES
Superiority Interaction
089 Intermediate (548-991)
075 (060-094)
104 (082-132) 076 0011
Centrersquos annual
volume of PCI
Low (247-544)
Intermediate (654-790)
Centrersquos
Proportion of
radial PCI
Low (149-644)
NSTE-ACS (tpndash) ACS type
STEMI
lt75 Age
ge75 023 088 (070-109)
082 (068-097) 0023 062
NACE Subgroup Analysis
High (1000-1950)
High (800-980)
NSTE-ACS (tp+)
Men Sex
Women
lt25 BMI
ge25
No
Ticagrelor or
prasugrel Yes
No Diabetes
Yes
lt60 GFR
ge60
No
History of
PVD Yes
2 025 050
075 (058-097) 0025
00048
101 (079-129)
095 (075 -122) 071
095
064 (051-080) lt0001
044
086 (068-108)
058 (033-103) 0059
019
085 (071-102) 007
0012 072 (056-093)
089 (076-105) 016 018
009 086 (073-102)
079 (063-099) 0038 053
007 083 (068-102)
084 (070-101) 006 094
045 091 (071-117)
080 (068-094) 008 043
001 078 (065-094)
086 (070-107) 018 051
060 091 (064-130)
083 (071-096) 0012 064
Radial Better Femoral Better 1
HAZARD RATIO (95 CI)
P-VALUES
Superiority Interaction
Intermediate (654-790)
Centrersquos
Proportion
of radial PCI
Low (149-644)
NSTE-ACS (tpndash) ACS
type
STEMI
Subgroup Analysis
High (800-980)
NSTE-ACS (tp+)
2
00157
128 (071-232)
069 (040 -119) 018
041
048 (028-081) 0006
010
087 (059-129) 049
049 (028-087) 0012
Intermediate (654-790) Centrersquos
Proportion
of radial PCI
Low (149-644)
NSTE-ACS (tpndash) ACS
type
STEMI
High (800-980)
NSTE-ACS (tp+)
020
090 (054-150)
057 (031 -103) 006
068
056 (032-097) 0035
054
062 (041-094)
166 (028-100) 058
0022
070 (042-117) 017
Mortality
Bleeding
4 050 025
1 2 050 025
Updated Meta-analysis 19328 ACS patients being randomly allocated to radial or femoral access
Rardial Better Femoral Better 1 4 025 050 2
Pre-Rival RIVAL Post-RIVAL MATRI
X Combined
Non-CABG
major bleeds
Death
myocardial
infarction or
stroke
Death
Myocardial
Infarction
Stroke
Pre-Rival RIVAL Post-RIVAL MATRI
X Combined
Pre-Rival RIVAL Post-RIVAL MATRI
X Combined
Pre-Rival RIVAL Post-RIVAL MATRI
X Combined
Pre-Rival RIVAL Post-RIVAL MATRI
X Combined
SUBGROUP Risk Ratio (95CI) P Value
Heterogenity
P Value I2
073 (043-123) 039 (023-067)
058 (046-072)
041 (022-076)
lt00001 0 05
1
067 (048-093) 086 (076-098) 086 (077-095)
098 (076-127)
00051 0 09
7
058 (039-087) 073 (053-099) 072 (060-088) 00011 0 10
0
085 (039-190) 091 (078-106) 091 (079-104)
092 (065-131)
01
6 0 08
8
068 (049-092)
082 (052-129)
077 (046-128) 086 (058-129)
073 (012-447)
140 (045-440) 100 (050-200) 105 (069-160)
143 (072-283)
08
0 0 07
5
026 (006-123)
Summary bull Among patients with an ACS with or without ST-segment
elevation who underwent invasive management the use
of radial access for coronary angiography plusmn PCI reduced
the rate of net adverse clinical events with a number
needed to treat for benefit of 53
ndash Differences between groups were driven by reductions in BARC
major bleeding unrelated to CABG and all-cause mortality with
radial access
bull Our results in conjunction with the updated meta-
analysis suggest that radial approach should
become the default access for patients with
ACS undergoing invasive management
Radial Acces 61000 menos Muertes
LA VIA TRANSRADIAL DEBERIA SER EL ACCESO DE ELECCION o ldquo DEFAULTrdquo PARA LOS PACIENTES CON SCA TRATADOS CON INTERVENCIONISMO PERCUTANEO
LA VIA TRANSRADIAL DEBERIA SER EL ACCESO DE ELECCION PARA TODO PACIENTE CONSIN SCA TRATADOS CON INTERVENCIONISMO PERCUTANEO
GRACIAS POR SU ATENCION
MACE
Mortality
No interaction between access and anticoagulant use in a post- hoc analysis of the subgroup of 7213 patients randomized to bivalirudin or unfractionated heparin for the two co-primary outcomes all-cause mortality or BARC 3 or 5 bleeding
Relevance of bleeding as a clinical endpoint
bull Availability of potent antithrombotic therapy including ndash ASA ndash P2Y12 inhibitors (clopidogrel prasugrel ticagrelor) ndash heparin ndash GP IIbIIIa inhibitors ndash direct thrombin inhibitors
bull has led to a reduction in ischemic events bull but is associated with an increased risk of
bleeding bull the increase in bleeding is associated with worse
clinical outcome
Rationale for a new bleeding definition
bull Increased importance of bleeding as prognostic factor
bull Need for assessment of bleeding in RCTs and registries
bull Lack of comparability bull Need for standardized definitions to avoid
erroneous conclusions
ndash regarding safety of a given agent ndash regarding superiority of one agent over another
Open questions regarding BARC
bull Why 48-hour window for CABG-related bleeding
bull Why type 1 bdquonot actionableldquo when patient may bdquotake actionldquo such as discontinuing medication (with potentially serious consequences such as ST)
bull Why consider intraocular bleed equivalent to intracranial bleed for BARC 3c
bull Type 1 bleed subject to misinterpretation by the patient
Hicks et al (editorial) Circulation 20111232664
Conclusion
bull BARC is a new objective hierarchically graded classification of bleeding
(Mehran Circulation [June 14] 20111232736)
bull BARC is based on consensus rather than data-driven
bull Prospective validation is warranted ndash across the spectrum of IHD
ndash across management strategies (conservative invasive)
ndash in the context of all invasive procedures (PCI CABG endovascular TAVI)
Conclusion (2)
bull Final validation of BARC and proof of its utility depend on
ndash its use by all future RCTs as common safety endpoint
ndash unanimous assessment procedure (questionnaires)
bull More important than using one or the other bleeding risk score is the agreement and commitment among clinical trialists to use the same score for comparability of data
Rardial Better Femoral Better 1
HAZARD RATIO (95 CI)
P-VALUES
Superiority Interaction
089 Intermediate (548-991)
075 (060-094)
104 (082-132) 076 0011
Centrersquos annual
volume of PCI
Low (247-544)
Intermediate (654-790)
Centrersquos
Proportion of
radial PCI
Low (149-644)
NSTE-ACS (tpndash) ACS type
STEMI
lt75 Age
ge75 023 088 (070-109)
082 (068-097) 0023 062
NACE Subgroup Analysis
High (1000-1950)
High (800-980)
NSTE-ACS (tp+)
Men Sex
Women
lt25 BMI
ge25
No
Ticagrelor or
prasugrel Yes
No Diabetes
Yes
lt60 GFR
ge60
No
History of
PVD Yes
2 025 050
075 (058-097) 0025
00048
101 (079-129)
095 (075 -122) 071
095
064 (051-080) lt0001
044
086 (068-108)
058 (033-103) 0059
019
085 (071-102) 007
0012 072 (056-093)
089 (076-105) 016 018
009 086 (073-102)
079 (063-099) 0038 053
007 083 (068-102)
084 (070-101) 006 094
045 091 (071-117)
080 (068-094) 008 043
001 078 (065-094)
086 (070-107) 018 051
060 091 (064-130)
083 (071-096) 0012 064
Radial Better Femoral Better 1
HAZARD RATIO (95 CI)
P-VALUES
Superiority Interaction
Intermediate (654-790)
Centrersquos
Proportion
of radial PCI
Low (149-644)
NSTE-ACS (tpndash) ACS
type
STEMI
Subgroup Analysis
High (800-980)
NSTE-ACS (tp+)
2
00157
128 (071-232)
069 (040 -119) 018
041
048 (028-081) 0006
010
087 (059-129) 049
049 (028-087) 0012
Intermediate (654-790) Centrersquos
Proportion
of radial PCI
Low (149-644)
NSTE-ACS (tpndash) ACS
type
STEMI
High (800-980)
NSTE-ACS (tp+)
020
090 (054-150)
057 (031 -103) 006
068
056 (032-097) 0035
054
062 (041-094)
166 (028-100) 058
0022
070 (042-117) 017
Mortality
Bleeding
4 050 025
1 2 050 025
Updated Meta-analysis 19328 ACS patients being randomly allocated to radial or femoral access
Rardial Better Femoral Better 1 4 025 050 2
Pre-Rival RIVAL Post-RIVAL MATRI
X Combined
Non-CABG
major bleeds
Death
myocardial
infarction or
stroke
Death
Myocardial
Infarction
Stroke
Pre-Rival RIVAL Post-RIVAL MATRI
X Combined
Pre-Rival RIVAL Post-RIVAL MATRI
X Combined
Pre-Rival RIVAL Post-RIVAL MATRI
X Combined
Pre-Rival RIVAL Post-RIVAL MATRI
X Combined
SUBGROUP Risk Ratio (95CI) P Value
Heterogenity
P Value I2
073 (043-123) 039 (023-067)
058 (046-072)
041 (022-076)
lt00001 0 05
1
067 (048-093) 086 (076-098) 086 (077-095)
098 (076-127)
00051 0 09
7
058 (039-087) 073 (053-099) 072 (060-088) 00011 0 10
0
085 (039-190) 091 (078-106) 091 (079-104)
092 (065-131)
01
6 0 08
8
068 (049-092)
082 (052-129)
077 (046-128) 086 (058-129)
073 (012-447)
140 (045-440) 100 (050-200) 105 (069-160)
143 (072-283)
08
0 0 07
5
026 (006-123)
Summary bull Among patients with an ACS with or without ST-segment
elevation who underwent invasive management the use
of radial access for coronary angiography plusmn PCI reduced
the rate of net adverse clinical events with a number
needed to treat for benefit of 53
ndash Differences between groups were driven by reductions in BARC
major bleeding unrelated to CABG and all-cause mortality with
radial access
bull Our results in conjunction with the updated meta-
analysis suggest that radial approach should
become the default access for patients with
ACS undergoing invasive management
Radial Acces 61000 menos Muertes
LA VIA TRANSRADIAL DEBERIA SER EL ACCESO DE ELECCION o ldquo DEFAULTrdquo PARA LOS PACIENTES CON SCA TRATADOS CON INTERVENCIONISMO PERCUTANEO
LA VIA TRANSRADIAL DEBERIA SER EL ACCESO DE ELECCION PARA TODO PACIENTE CONSIN SCA TRATADOS CON INTERVENCIONISMO PERCUTANEO
GRACIAS POR SU ATENCION
MACE
Mortality
No interaction between access and anticoagulant use in a post- hoc analysis of the subgroup of 7213 patients randomized to bivalirudin or unfractionated heparin for the two co-primary outcomes all-cause mortality or BARC 3 or 5 bleeding
Relevance of bleeding as a clinical endpoint
bull Availability of potent antithrombotic therapy including ndash ASA ndash P2Y12 inhibitors (clopidogrel prasugrel ticagrelor) ndash heparin ndash GP IIbIIIa inhibitors ndash direct thrombin inhibitors
bull has led to a reduction in ischemic events bull but is associated with an increased risk of
bleeding bull the increase in bleeding is associated with worse
clinical outcome
Rationale for a new bleeding definition
bull Increased importance of bleeding as prognostic factor
bull Need for assessment of bleeding in RCTs and registries
bull Lack of comparability bull Need for standardized definitions to avoid
erroneous conclusions
ndash regarding safety of a given agent ndash regarding superiority of one agent over another
Open questions regarding BARC
bull Why 48-hour window for CABG-related bleeding
bull Why type 1 bdquonot actionableldquo when patient may bdquotake actionldquo such as discontinuing medication (with potentially serious consequences such as ST)
bull Why consider intraocular bleed equivalent to intracranial bleed for BARC 3c
bull Type 1 bleed subject to misinterpretation by the patient
Hicks et al (editorial) Circulation 20111232664
Conclusion
bull BARC is a new objective hierarchically graded classification of bleeding
(Mehran Circulation [June 14] 20111232736)
bull BARC is based on consensus rather than data-driven
bull Prospective validation is warranted ndash across the spectrum of IHD
ndash across management strategies (conservative invasive)
ndash in the context of all invasive procedures (PCI CABG endovascular TAVI)
Conclusion (2)
bull Final validation of BARC and proof of its utility depend on
ndash its use by all future RCTs as common safety endpoint
ndash unanimous assessment procedure (questionnaires)
bull More important than using one or the other bleeding risk score is the agreement and commitment among clinical trialists to use the same score for comparability of data
Radial Better Femoral Better 1
HAZARD RATIO (95 CI)
P-VALUES
Superiority Interaction
Intermediate (654-790)
Centrersquos
Proportion
of radial PCI
Low (149-644)
NSTE-ACS (tpndash) ACS
type
STEMI
Subgroup Analysis
High (800-980)
NSTE-ACS (tp+)
2
00157
128 (071-232)
069 (040 -119) 018
041
048 (028-081) 0006
010
087 (059-129) 049
049 (028-087) 0012
Intermediate (654-790) Centrersquos
Proportion
of radial PCI
Low (149-644)
NSTE-ACS (tpndash) ACS
type
STEMI
High (800-980)
NSTE-ACS (tp+)
020
090 (054-150)
057 (031 -103) 006
068
056 (032-097) 0035
054
062 (041-094)
166 (028-100) 058
0022
070 (042-117) 017
Mortality
Bleeding
4 050 025
1 2 050 025
Updated Meta-analysis 19328 ACS patients being randomly allocated to radial or femoral access
Rardial Better Femoral Better 1 4 025 050 2
Pre-Rival RIVAL Post-RIVAL MATRI
X Combined
Non-CABG
major bleeds
Death
myocardial
infarction or
stroke
Death
Myocardial
Infarction
Stroke
Pre-Rival RIVAL Post-RIVAL MATRI
X Combined
Pre-Rival RIVAL Post-RIVAL MATRI
X Combined
Pre-Rival RIVAL Post-RIVAL MATRI
X Combined
Pre-Rival RIVAL Post-RIVAL MATRI
X Combined
SUBGROUP Risk Ratio (95CI) P Value
Heterogenity
P Value I2
073 (043-123) 039 (023-067)
058 (046-072)
041 (022-076)
lt00001 0 05
1
067 (048-093) 086 (076-098) 086 (077-095)
098 (076-127)
00051 0 09
7
058 (039-087) 073 (053-099) 072 (060-088) 00011 0 10
0
085 (039-190) 091 (078-106) 091 (079-104)
092 (065-131)
01
6 0 08
8
068 (049-092)
082 (052-129)
077 (046-128) 086 (058-129)
073 (012-447)
140 (045-440) 100 (050-200) 105 (069-160)
143 (072-283)
08
0 0 07
5
026 (006-123)
Summary bull Among patients with an ACS with or without ST-segment
elevation who underwent invasive management the use
of radial access for coronary angiography plusmn PCI reduced
the rate of net adverse clinical events with a number
needed to treat for benefit of 53
ndash Differences between groups were driven by reductions in BARC
major bleeding unrelated to CABG and all-cause mortality with
radial access
bull Our results in conjunction with the updated meta-
analysis suggest that radial approach should
become the default access for patients with
ACS undergoing invasive management
Radial Acces 61000 menos Muertes
LA VIA TRANSRADIAL DEBERIA SER EL ACCESO DE ELECCION o ldquo DEFAULTrdquo PARA LOS PACIENTES CON SCA TRATADOS CON INTERVENCIONISMO PERCUTANEO
LA VIA TRANSRADIAL DEBERIA SER EL ACCESO DE ELECCION PARA TODO PACIENTE CONSIN SCA TRATADOS CON INTERVENCIONISMO PERCUTANEO
GRACIAS POR SU ATENCION
MACE
Mortality
No interaction between access and anticoagulant use in a post- hoc analysis of the subgroup of 7213 patients randomized to bivalirudin or unfractionated heparin for the two co-primary outcomes all-cause mortality or BARC 3 or 5 bleeding
Relevance of bleeding as a clinical endpoint
bull Availability of potent antithrombotic therapy including ndash ASA ndash P2Y12 inhibitors (clopidogrel prasugrel ticagrelor) ndash heparin ndash GP IIbIIIa inhibitors ndash direct thrombin inhibitors
bull has led to a reduction in ischemic events bull but is associated with an increased risk of
bleeding bull the increase in bleeding is associated with worse
clinical outcome
Rationale for a new bleeding definition
bull Increased importance of bleeding as prognostic factor
bull Need for assessment of bleeding in RCTs and registries
bull Lack of comparability bull Need for standardized definitions to avoid
erroneous conclusions
ndash regarding safety of a given agent ndash regarding superiority of one agent over another
Open questions regarding BARC
bull Why 48-hour window for CABG-related bleeding
bull Why type 1 bdquonot actionableldquo when patient may bdquotake actionldquo such as discontinuing medication (with potentially serious consequences such as ST)
bull Why consider intraocular bleed equivalent to intracranial bleed for BARC 3c
bull Type 1 bleed subject to misinterpretation by the patient
Hicks et al (editorial) Circulation 20111232664
Conclusion
bull BARC is a new objective hierarchically graded classification of bleeding
(Mehran Circulation [June 14] 20111232736)
bull BARC is based on consensus rather than data-driven
bull Prospective validation is warranted ndash across the spectrum of IHD
ndash across management strategies (conservative invasive)
ndash in the context of all invasive procedures (PCI CABG endovascular TAVI)
Conclusion (2)
bull Final validation of BARC and proof of its utility depend on
ndash its use by all future RCTs as common safety endpoint
ndash unanimous assessment procedure (questionnaires)
bull More important than using one or the other bleeding risk score is the agreement and commitment among clinical trialists to use the same score for comparability of data
Updated Meta-analysis 19328 ACS patients being randomly allocated to radial or femoral access
Rardial Better Femoral Better 1 4 025 050 2
Pre-Rival RIVAL Post-RIVAL MATRI
X Combined
Non-CABG
major bleeds
Death
myocardial
infarction or
stroke
Death
Myocardial
Infarction
Stroke
Pre-Rival RIVAL Post-RIVAL MATRI
X Combined
Pre-Rival RIVAL Post-RIVAL MATRI
X Combined
Pre-Rival RIVAL Post-RIVAL MATRI
X Combined
Pre-Rival RIVAL Post-RIVAL MATRI
X Combined
SUBGROUP Risk Ratio (95CI) P Value
Heterogenity
P Value I2
073 (043-123) 039 (023-067)
058 (046-072)
041 (022-076)
lt00001 0 05
1
067 (048-093) 086 (076-098) 086 (077-095)
098 (076-127)
00051 0 09
7
058 (039-087) 073 (053-099) 072 (060-088) 00011 0 10
0
085 (039-190) 091 (078-106) 091 (079-104)
092 (065-131)
01
6 0 08
8
068 (049-092)
082 (052-129)
077 (046-128) 086 (058-129)
073 (012-447)
140 (045-440) 100 (050-200) 105 (069-160)
143 (072-283)
08
0 0 07
5
026 (006-123)
Summary bull Among patients with an ACS with or without ST-segment
elevation who underwent invasive management the use
of radial access for coronary angiography plusmn PCI reduced
the rate of net adverse clinical events with a number
needed to treat for benefit of 53
ndash Differences between groups were driven by reductions in BARC
major bleeding unrelated to CABG and all-cause mortality with
radial access
bull Our results in conjunction with the updated meta-
analysis suggest that radial approach should
become the default access for patients with
ACS undergoing invasive management
Radial Acces 61000 menos Muertes
LA VIA TRANSRADIAL DEBERIA SER EL ACCESO DE ELECCION o ldquo DEFAULTrdquo PARA LOS PACIENTES CON SCA TRATADOS CON INTERVENCIONISMO PERCUTANEO
LA VIA TRANSRADIAL DEBERIA SER EL ACCESO DE ELECCION PARA TODO PACIENTE CONSIN SCA TRATADOS CON INTERVENCIONISMO PERCUTANEO
GRACIAS POR SU ATENCION
MACE
Mortality
No interaction between access and anticoagulant use in a post- hoc analysis of the subgroup of 7213 patients randomized to bivalirudin or unfractionated heparin for the two co-primary outcomes all-cause mortality or BARC 3 or 5 bleeding
Relevance of bleeding as a clinical endpoint
bull Availability of potent antithrombotic therapy including ndash ASA ndash P2Y12 inhibitors (clopidogrel prasugrel ticagrelor) ndash heparin ndash GP IIbIIIa inhibitors ndash direct thrombin inhibitors
bull has led to a reduction in ischemic events bull but is associated with an increased risk of
bleeding bull the increase in bleeding is associated with worse
clinical outcome
Rationale for a new bleeding definition
bull Increased importance of bleeding as prognostic factor
bull Need for assessment of bleeding in RCTs and registries
bull Lack of comparability bull Need for standardized definitions to avoid
erroneous conclusions
ndash regarding safety of a given agent ndash regarding superiority of one agent over another
Open questions regarding BARC
bull Why 48-hour window for CABG-related bleeding
bull Why type 1 bdquonot actionableldquo when patient may bdquotake actionldquo such as discontinuing medication (with potentially serious consequences such as ST)
bull Why consider intraocular bleed equivalent to intracranial bleed for BARC 3c
bull Type 1 bleed subject to misinterpretation by the patient
Hicks et al (editorial) Circulation 20111232664
Conclusion
bull BARC is a new objective hierarchically graded classification of bleeding
(Mehran Circulation [June 14] 20111232736)
bull BARC is based on consensus rather than data-driven
bull Prospective validation is warranted ndash across the spectrum of IHD
ndash across management strategies (conservative invasive)
ndash in the context of all invasive procedures (PCI CABG endovascular TAVI)
Conclusion (2)
bull Final validation of BARC and proof of its utility depend on
ndash its use by all future RCTs as common safety endpoint
ndash unanimous assessment procedure (questionnaires)
bull More important than using one or the other bleeding risk score is the agreement and commitment among clinical trialists to use the same score for comparability of data
Summary bull Among patients with an ACS with or without ST-segment
elevation who underwent invasive management the use
of radial access for coronary angiography plusmn PCI reduced
the rate of net adverse clinical events with a number
needed to treat for benefit of 53
ndash Differences between groups were driven by reductions in BARC
major bleeding unrelated to CABG and all-cause mortality with
radial access
bull Our results in conjunction with the updated meta-
analysis suggest that radial approach should
become the default access for patients with
ACS undergoing invasive management
Radial Acces 61000 menos Muertes
LA VIA TRANSRADIAL DEBERIA SER EL ACCESO DE ELECCION o ldquo DEFAULTrdquo PARA LOS PACIENTES CON SCA TRATADOS CON INTERVENCIONISMO PERCUTANEO
LA VIA TRANSRADIAL DEBERIA SER EL ACCESO DE ELECCION PARA TODO PACIENTE CONSIN SCA TRATADOS CON INTERVENCIONISMO PERCUTANEO
GRACIAS POR SU ATENCION
MACE
Mortality
No interaction between access and anticoagulant use in a post- hoc analysis of the subgroup of 7213 patients randomized to bivalirudin or unfractionated heparin for the two co-primary outcomes all-cause mortality or BARC 3 or 5 bleeding
Relevance of bleeding as a clinical endpoint
bull Availability of potent antithrombotic therapy including ndash ASA ndash P2Y12 inhibitors (clopidogrel prasugrel ticagrelor) ndash heparin ndash GP IIbIIIa inhibitors ndash direct thrombin inhibitors
bull has led to a reduction in ischemic events bull but is associated with an increased risk of
bleeding bull the increase in bleeding is associated with worse
clinical outcome
Rationale for a new bleeding definition
bull Increased importance of bleeding as prognostic factor
bull Need for assessment of bleeding in RCTs and registries
bull Lack of comparability bull Need for standardized definitions to avoid
erroneous conclusions
ndash regarding safety of a given agent ndash regarding superiority of one agent over another
Open questions regarding BARC
bull Why 48-hour window for CABG-related bleeding
bull Why type 1 bdquonot actionableldquo when patient may bdquotake actionldquo such as discontinuing medication (with potentially serious consequences such as ST)
bull Why consider intraocular bleed equivalent to intracranial bleed for BARC 3c
bull Type 1 bleed subject to misinterpretation by the patient
Hicks et al (editorial) Circulation 20111232664
Conclusion
bull BARC is a new objective hierarchically graded classification of bleeding
(Mehran Circulation [June 14] 20111232736)
bull BARC is based on consensus rather than data-driven
bull Prospective validation is warranted ndash across the spectrum of IHD
ndash across management strategies (conservative invasive)
ndash in the context of all invasive procedures (PCI CABG endovascular TAVI)
Conclusion (2)
bull Final validation of BARC and proof of its utility depend on
ndash its use by all future RCTs as common safety endpoint
ndash unanimous assessment procedure (questionnaires)
bull More important than using one or the other bleeding risk score is the agreement and commitment among clinical trialists to use the same score for comparability of data
LA VIA TRANSRADIAL DEBERIA SER EL ACCESO DE ELECCION o ldquo DEFAULTrdquo PARA LOS PACIENTES CON SCA TRATADOS CON INTERVENCIONISMO PERCUTANEO
LA VIA TRANSRADIAL DEBERIA SER EL ACCESO DE ELECCION PARA TODO PACIENTE CONSIN SCA TRATADOS CON INTERVENCIONISMO PERCUTANEO
GRACIAS POR SU ATENCION
MACE
Mortality
No interaction between access and anticoagulant use in a post- hoc analysis of the subgroup of 7213 patients randomized to bivalirudin or unfractionated heparin for the two co-primary outcomes all-cause mortality or BARC 3 or 5 bleeding
Relevance of bleeding as a clinical endpoint
bull Availability of potent antithrombotic therapy including ndash ASA ndash P2Y12 inhibitors (clopidogrel prasugrel ticagrelor) ndash heparin ndash GP IIbIIIa inhibitors ndash direct thrombin inhibitors
bull has led to a reduction in ischemic events bull but is associated with an increased risk of
bleeding bull the increase in bleeding is associated with worse
clinical outcome
Rationale for a new bleeding definition
bull Increased importance of bleeding as prognostic factor
bull Need for assessment of bleeding in RCTs and registries
bull Lack of comparability bull Need for standardized definitions to avoid
erroneous conclusions
ndash regarding safety of a given agent ndash regarding superiority of one agent over another
Open questions regarding BARC
bull Why 48-hour window for CABG-related bleeding
bull Why type 1 bdquonot actionableldquo when patient may bdquotake actionldquo such as discontinuing medication (with potentially serious consequences such as ST)
bull Why consider intraocular bleed equivalent to intracranial bleed for BARC 3c
bull Type 1 bleed subject to misinterpretation by the patient
Hicks et al (editorial) Circulation 20111232664
Conclusion
bull BARC is a new objective hierarchically graded classification of bleeding
(Mehran Circulation [June 14] 20111232736)
bull BARC is based on consensus rather than data-driven
bull Prospective validation is warranted ndash across the spectrum of IHD
ndash across management strategies (conservative invasive)
ndash in the context of all invasive procedures (PCI CABG endovascular TAVI)
Conclusion (2)
bull Final validation of BARC and proof of its utility depend on
ndash its use by all future RCTs as common safety endpoint
ndash unanimous assessment procedure (questionnaires)
bull More important than using one or the other bleeding risk score is the agreement and commitment among clinical trialists to use the same score for comparability of data
LA VIA TRANSRADIAL DEBERIA SER EL ACCESO DE ELECCION PARA TODO PACIENTE CONSIN SCA TRATADOS CON INTERVENCIONISMO PERCUTANEO
GRACIAS POR SU ATENCION
MACE
Mortality
No interaction between access and anticoagulant use in a post- hoc analysis of the subgroup of 7213 patients randomized to bivalirudin or unfractionated heparin for the two co-primary outcomes all-cause mortality or BARC 3 or 5 bleeding
Relevance of bleeding as a clinical endpoint
bull Availability of potent antithrombotic therapy including ndash ASA ndash P2Y12 inhibitors (clopidogrel prasugrel ticagrelor) ndash heparin ndash GP IIbIIIa inhibitors ndash direct thrombin inhibitors
bull has led to a reduction in ischemic events bull but is associated with an increased risk of
bleeding bull the increase in bleeding is associated with worse
clinical outcome
Rationale for a new bleeding definition
bull Increased importance of bleeding as prognostic factor
bull Need for assessment of bleeding in RCTs and registries
bull Lack of comparability bull Need for standardized definitions to avoid
erroneous conclusions
ndash regarding safety of a given agent ndash regarding superiority of one agent over another
Open questions regarding BARC
bull Why 48-hour window for CABG-related bleeding
bull Why type 1 bdquonot actionableldquo when patient may bdquotake actionldquo such as discontinuing medication (with potentially serious consequences such as ST)
bull Why consider intraocular bleed equivalent to intracranial bleed for BARC 3c
bull Type 1 bleed subject to misinterpretation by the patient
Hicks et al (editorial) Circulation 20111232664
Conclusion
bull BARC is a new objective hierarchically graded classification of bleeding
(Mehran Circulation [June 14] 20111232736)
bull BARC is based on consensus rather than data-driven
bull Prospective validation is warranted ndash across the spectrum of IHD
ndash across management strategies (conservative invasive)
ndash in the context of all invasive procedures (PCI CABG endovascular TAVI)
Conclusion (2)
bull Final validation of BARC and proof of its utility depend on
ndash its use by all future RCTs as common safety endpoint
ndash unanimous assessment procedure (questionnaires)
bull More important than using one or the other bleeding risk score is the agreement and commitment among clinical trialists to use the same score for comparability of data
GRACIAS POR SU ATENCION
MACE
Mortality
No interaction between access and anticoagulant use in a post- hoc analysis of the subgroup of 7213 patients randomized to bivalirudin or unfractionated heparin for the two co-primary outcomes all-cause mortality or BARC 3 or 5 bleeding
Relevance of bleeding as a clinical endpoint
bull Availability of potent antithrombotic therapy including ndash ASA ndash P2Y12 inhibitors (clopidogrel prasugrel ticagrelor) ndash heparin ndash GP IIbIIIa inhibitors ndash direct thrombin inhibitors
bull has led to a reduction in ischemic events bull but is associated with an increased risk of
bleeding bull the increase in bleeding is associated with worse
clinical outcome
Rationale for a new bleeding definition
bull Increased importance of bleeding as prognostic factor
bull Need for assessment of bleeding in RCTs and registries
bull Lack of comparability bull Need for standardized definitions to avoid
erroneous conclusions
ndash regarding safety of a given agent ndash regarding superiority of one agent over another
Open questions regarding BARC
bull Why 48-hour window for CABG-related bleeding
bull Why type 1 bdquonot actionableldquo when patient may bdquotake actionldquo such as discontinuing medication (with potentially serious consequences such as ST)
bull Why consider intraocular bleed equivalent to intracranial bleed for BARC 3c
bull Type 1 bleed subject to misinterpretation by the patient
Hicks et al (editorial) Circulation 20111232664
Conclusion
bull BARC is a new objective hierarchically graded classification of bleeding
(Mehran Circulation [June 14] 20111232736)
bull BARC is based on consensus rather than data-driven
bull Prospective validation is warranted ndash across the spectrum of IHD
ndash across management strategies (conservative invasive)
ndash in the context of all invasive procedures (PCI CABG endovascular TAVI)
Conclusion (2)
bull Final validation of BARC and proof of its utility depend on
ndash its use by all future RCTs as common safety endpoint
ndash unanimous assessment procedure (questionnaires)
bull More important than using one or the other bleeding risk score is the agreement and commitment among clinical trialists to use the same score for comparability of data
MACE
Mortality
No interaction between access and anticoagulant use in a post- hoc analysis of the subgroup of 7213 patients randomized to bivalirudin or unfractionated heparin for the two co-primary outcomes all-cause mortality or BARC 3 or 5 bleeding
Relevance of bleeding as a clinical endpoint
bull Availability of potent antithrombotic therapy including ndash ASA ndash P2Y12 inhibitors (clopidogrel prasugrel ticagrelor) ndash heparin ndash GP IIbIIIa inhibitors ndash direct thrombin inhibitors
bull has led to a reduction in ischemic events bull but is associated with an increased risk of
bleeding bull the increase in bleeding is associated with worse
clinical outcome
Rationale for a new bleeding definition
bull Increased importance of bleeding as prognostic factor
bull Need for assessment of bleeding in RCTs and registries
bull Lack of comparability bull Need for standardized definitions to avoid
erroneous conclusions
ndash regarding safety of a given agent ndash regarding superiority of one agent over another
Open questions regarding BARC
bull Why 48-hour window for CABG-related bleeding
bull Why type 1 bdquonot actionableldquo when patient may bdquotake actionldquo such as discontinuing medication (with potentially serious consequences such as ST)
bull Why consider intraocular bleed equivalent to intracranial bleed for BARC 3c
bull Type 1 bleed subject to misinterpretation by the patient
Hicks et al (editorial) Circulation 20111232664
Conclusion
bull BARC is a new objective hierarchically graded classification of bleeding
(Mehran Circulation [June 14] 20111232736)
bull BARC is based on consensus rather than data-driven
bull Prospective validation is warranted ndash across the spectrum of IHD
ndash across management strategies (conservative invasive)
ndash in the context of all invasive procedures (PCI CABG endovascular TAVI)
Conclusion (2)
bull Final validation of BARC and proof of its utility depend on
ndash its use by all future RCTs as common safety endpoint
ndash unanimous assessment procedure (questionnaires)
bull More important than using one or the other bleeding risk score is the agreement and commitment among clinical trialists to use the same score for comparability of data
No interaction between access and anticoagulant use in a post- hoc analysis of the subgroup of 7213 patients randomized to bivalirudin or unfractionated heparin for the two co-primary outcomes all-cause mortality or BARC 3 or 5 bleeding
Relevance of bleeding as a clinical endpoint
bull Availability of potent antithrombotic therapy including ndash ASA ndash P2Y12 inhibitors (clopidogrel prasugrel ticagrelor) ndash heparin ndash GP IIbIIIa inhibitors ndash direct thrombin inhibitors
bull has led to a reduction in ischemic events bull but is associated with an increased risk of
bleeding bull the increase in bleeding is associated with worse
clinical outcome
Rationale for a new bleeding definition
bull Increased importance of bleeding as prognostic factor
bull Need for assessment of bleeding in RCTs and registries
bull Lack of comparability bull Need for standardized definitions to avoid
erroneous conclusions
ndash regarding safety of a given agent ndash regarding superiority of one agent over another
Open questions regarding BARC
bull Why 48-hour window for CABG-related bleeding
bull Why type 1 bdquonot actionableldquo when patient may bdquotake actionldquo such as discontinuing medication (with potentially serious consequences such as ST)
bull Why consider intraocular bleed equivalent to intracranial bleed for BARC 3c
bull Type 1 bleed subject to misinterpretation by the patient
Hicks et al (editorial) Circulation 20111232664
Conclusion
bull BARC is a new objective hierarchically graded classification of bleeding
(Mehran Circulation [June 14] 20111232736)
bull BARC is based on consensus rather than data-driven
bull Prospective validation is warranted ndash across the spectrum of IHD
ndash across management strategies (conservative invasive)
ndash in the context of all invasive procedures (PCI CABG endovascular TAVI)
Conclusion (2)
bull Final validation of BARC and proof of its utility depend on
ndash its use by all future RCTs as common safety endpoint
ndash unanimous assessment procedure (questionnaires)
bull More important than using one or the other bleeding risk score is the agreement and commitment among clinical trialists to use the same score for comparability of data
Relevance of bleeding as a clinical endpoint
bull Availability of potent antithrombotic therapy including ndash ASA ndash P2Y12 inhibitors (clopidogrel prasugrel ticagrelor) ndash heparin ndash GP IIbIIIa inhibitors ndash direct thrombin inhibitors
bull has led to a reduction in ischemic events bull but is associated with an increased risk of
bleeding bull the increase in bleeding is associated with worse
clinical outcome
Rationale for a new bleeding definition
bull Increased importance of bleeding as prognostic factor
bull Need for assessment of bleeding in RCTs and registries
bull Lack of comparability bull Need for standardized definitions to avoid
erroneous conclusions
ndash regarding safety of a given agent ndash regarding superiority of one agent over another
Open questions regarding BARC
bull Why 48-hour window for CABG-related bleeding
bull Why type 1 bdquonot actionableldquo when patient may bdquotake actionldquo such as discontinuing medication (with potentially serious consequences such as ST)
bull Why consider intraocular bleed equivalent to intracranial bleed for BARC 3c
bull Type 1 bleed subject to misinterpretation by the patient
Hicks et al (editorial) Circulation 20111232664
Conclusion
bull BARC is a new objective hierarchically graded classification of bleeding
(Mehran Circulation [June 14] 20111232736)
bull BARC is based on consensus rather than data-driven
bull Prospective validation is warranted ndash across the spectrum of IHD
ndash across management strategies (conservative invasive)
ndash in the context of all invasive procedures (PCI CABG endovascular TAVI)
Conclusion (2)
bull Final validation of BARC and proof of its utility depend on
ndash its use by all future RCTs as common safety endpoint
ndash unanimous assessment procedure (questionnaires)
bull More important than using one or the other bleeding risk score is the agreement and commitment among clinical trialists to use the same score for comparability of data
Rationale for a new bleeding definition
bull Increased importance of bleeding as prognostic factor
bull Need for assessment of bleeding in RCTs and registries
bull Lack of comparability bull Need for standardized definitions to avoid
erroneous conclusions
ndash regarding safety of a given agent ndash regarding superiority of one agent over another
Open questions regarding BARC
bull Why 48-hour window for CABG-related bleeding
bull Why type 1 bdquonot actionableldquo when patient may bdquotake actionldquo such as discontinuing medication (with potentially serious consequences such as ST)
bull Why consider intraocular bleed equivalent to intracranial bleed for BARC 3c
bull Type 1 bleed subject to misinterpretation by the patient
Hicks et al (editorial) Circulation 20111232664
Conclusion
bull BARC is a new objective hierarchically graded classification of bleeding
(Mehran Circulation [June 14] 20111232736)
bull BARC is based on consensus rather than data-driven
bull Prospective validation is warranted ndash across the spectrum of IHD
ndash across management strategies (conservative invasive)
ndash in the context of all invasive procedures (PCI CABG endovascular TAVI)
Conclusion (2)
bull Final validation of BARC and proof of its utility depend on
ndash its use by all future RCTs as common safety endpoint
ndash unanimous assessment procedure (questionnaires)
bull More important than using one or the other bleeding risk score is the agreement and commitment among clinical trialists to use the same score for comparability of data
Open questions regarding BARC
bull Why 48-hour window for CABG-related bleeding
bull Why type 1 bdquonot actionableldquo when patient may bdquotake actionldquo such as discontinuing medication (with potentially serious consequences such as ST)
bull Why consider intraocular bleed equivalent to intracranial bleed for BARC 3c
bull Type 1 bleed subject to misinterpretation by the patient
Hicks et al (editorial) Circulation 20111232664
Conclusion
bull BARC is a new objective hierarchically graded classification of bleeding
(Mehran Circulation [June 14] 20111232736)
bull BARC is based on consensus rather than data-driven
bull Prospective validation is warranted ndash across the spectrum of IHD
ndash across management strategies (conservative invasive)
ndash in the context of all invasive procedures (PCI CABG endovascular TAVI)
Conclusion (2)
bull Final validation of BARC and proof of its utility depend on
ndash its use by all future RCTs as common safety endpoint
ndash unanimous assessment procedure (questionnaires)
bull More important than using one or the other bleeding risk score is the agreement and commitment among clinical trialists to use the same score for comparability of data
Conclusion
bull BARC is a new objective hierarchically graded classification of bleeding
(Mehran Circulation [June 14] 20111232736)
bull BARC is based on consensus rather than data-driven
bull Prospective validation is warranted ndash across the spectrum of IHD
ndash across management strategies (conservative invasive)
ndash in the context of all invasive procedures (PCI CABG endovascular TAVI)
Conclusion (2)
bull Final validation of BARC and proof of its utility depend on
ndash its use by all future RCTs as common safety endpoint
ndash unanimous assessment procedure (questionnaires)
bull More important than using one or the other bleeding risk score is the agreement and commitment among clinical trialists to use the same score for comparability of data
Conclusion (2)
bull Final validation of BARC and proof of its utility depend on
ndash its use by all future RCTs as common safety endpoint
ndash unanimous assessment procedure (questionnaires)
bull More important than using one or the other bleeding risk score is the agreement and commitment among clinical trialists to use the same score for comparability of data
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