Actualités en cardiologie sur les SCA ST+ Guillaume LEURENT, CHU RENNES Parigné, le 23 Mai 2013

Actualités en cardiologie sur les SCA ST+

Guillaume LEURENT, CHU RENNES

Parigné, le 23 Mai 2013

Syndromes Coronaires Aigus ST +

« Nouvelles recommandations »Dernières

Eur Heart J 2012 JACC 2013

Pourquoi « revoir » nos protocoles de prise en charge ?

La mise sur le marché « récente » de « nouveaux »anti agrégants plaquettaires oraux

Clopidogrel Prasugrel Ticagrelor

PLAVIX® EFIENT® BRILIQUE®

La remise en cause du bénéfice de l’administration précoced’un anti GPIIbIIIa en amont de la salle de coronarographie

L’incertitude quant au type d’anti coagulant à utiliser

ECG qualifiantDiagnostic ST+

Une reperfusion est indiquée chez tous les patients avec une douleur de moins de 12 heures et un sus décalage persistant du segment ST (ou BBG présumé nouveau) [IA]

SMURPrise en chargeDouleur

Thor.

Reperfusion > 12 heures ?

• Une reperfusion doit être discutée si la douleur dure plus de 12 heures et qu’il persiste des signes cliniques (douleur persistante) ou électriques (sus décalage persistant) d’ischémie persistante [IIa, C]

• Une reperfusion peut être discutée si la douleur dure plus de 12 heures et moins de 24 heures chez un patient stable [IIb, B]

• Pas d’indication à dilater une artère occluse après la 24ème heure chez un patient stable sans signe d’ischémie [IIIB]

Quelle reperfusion ?

« L’angioplastie primaire est le traitement de reperfusionpréféré si réalisée par une équipe expérimentée dans les délais recommandés »

ESC 2012

Reco ESC 2012

Treatment Delay in Patients Undergoing Primary PCI for ST-Elevation Myocardial Infarction: Data from the Regional Acute Myocardial Infarction

Registry of Brittany (ORBI)

G. Leurent1, C. Fougerou2, P. Druelles3, E. Filippi4, B. Moquet5, PY Pennec6, JP Hacot7, A. Rialan8, G. Rouault9, R. Gervais1, D. Boulmier1, M. Bedossa1, H. Courcoux10, I. Coudert10, B. Boulanger11, C. Hamon12,

J. Treuil13, H. Le Breton1

1. Département de Cardiologie, Rennes; 2. Centre d’ Investigation Clinique, Rennes; 3. Service de Cardiologie, Clinique St Laurent, Rennes; 4. Département de Cardiologie, Vannes; 5. Département de Cardiologie, St Brieuc; 6. Département de

Cardiologie, Brest; 7. Département de Cardiologie, Lorient; 8. Département de Cardiologie, Saint Malo; 9. Département de Cardiologie, Quimper; 10. SAMU 35, Rennes; 11. SAMU 56, Vannes; 12. SAMU 22, St Brieuc; 13. SAMU 29, Brest.

Background: In the management of acute myocardial infarction (MI) treated by PCI, a delay of less than 90 mn is recommended. This delay can be divided in 2 parts: The pre-hospital delay and the intra-hospital delay, which is estimated close to 45 mn.

Objectives: To precise the intra-hospital delay (IHD) in the “real life” using the prospectively collected data of the French Brittany Survey on myocardial infarction (ORBI). Predictive factors of an IHD≤45 mn were studied, on purpose to optimize this IHD.

Methods: We analyzed data from 560 patients hospitalized in 8 French Brittany hospitals for an acute MI and treated by a primary PCI, on an 18 months period. Patients treated by a fibrinolysis or initially hospitalized in a secondary hospital were excluded. We prospectively collected data and performed uni and multivariate analysis of predictive factors of IHD ≤45 mn.

Results: Median delay between 1st medical contact and balloon inflation was 94 mn and ≤90 mn for only 35% of patients. Median IHD was 44mn and ≤45 mn for 52.8 % of patients. In univariate analysis, several factors were associated with an IHD ≤45 mn: male gender, short delay between onset of symptoms and first call, admission during working hours (8h-20h), a pre-hospital medical care, direct admission in the cath lab, SAMU as first contact,and the mobile care unit intervention. In the multivariate analysis, only 2 factors were significantly associated with an IHD≤45 mn: direct admission in the cath lab (312 patients): IHD = 34 mn vs 77 mn, p<0.001 and admission during working hours (371 patients): IHD = 40 mn vs 51 mn, p=0.004.

Conclusion: Intra-hospital median delay between admission and PCI in French Brittany is close to 45 mn, longer than 45 mn in half of patients. Delays are still too long and efforts should be done to reduce both pre-hospital and intra-hospital delays. A direct admission in the cath lab and admission during working hours are strongly associated with a short intra-hospital delay (≤45 mn). For further information: [email protected]

Onset ofsymptom

1st call50 mn50 mn

1st medicalintervention25 mn25 mn

Admission65 mn65 mn

PCI44 mn44 mn

34 mn34 mn

… direct to the cath lab’

… to ICU / triage departmt

Admission… PCI44 mn44 mn

77 mn77 mn

PCIAdmission…44 mn44 mn

… between 8am and 8pm

40 mn40 mn

… between 8pm and 8am

51 mn51 mn

Median delays

Median IHD according to place

and hours of admission

p<0.001 p=0.004

Mars 2013

Etude STREAM…

-Coro urgente nécessaire pour 36% des patients fibrinolysés

Quel ttt AAP avant angioplastie primaire ?

Reco ACC 2013

Reco ESC 2012

Quelle thiénopyridine associer à l’aspirine (500 mg IV) dans l’angioplastie primaire ?

9,9

12,1

2,1

2,47,3

9,5

1 11,1

2,4

p<0,001

p<0,001

p<0,001

Etude TRITON Prasugrel (EFIENT) vs Clopidogrel

13 608 patients dilatés dans le contexte d’un SCA (ST+ = 26%, ST- = 74%)

Wiviott S et al. N Engl J Med 2007;357:2001-2015

Reco ESC 2012

18 624 patients dilatés dans le contexte d’un SCA (ST+ = 37%, ST- = 63%)

Cayla G. Int J Cardiol 2013

Mortalité CV + IDM + stroke

Chez le diabétique…

Fereirro JL. Circulation 2011

Quel anticoagulant avant angioplastie primaire ?

Reco ESC 2012

Reco ACC 2013

• Fondaparinux

OASIS 6 Yusuf et al JAMA 2006;295:1519-30

Chez les patients dilatés, augmentation non significative de 1% du taux de décès ou réinfarctus à 30 jours

Ceci associé au risque de thrombose de catheter n’est pas en faveur de l’utilisation du fondaparinux comme seul anticoagulant dans l’angioplastie primaire


Reco ESC 2012

Reco ACC 2013

Lancet 2011


Reco ESC 2012

Reco ACC 2013

Voie radiale: n=200 vs voie fémorale: n=3134…

Place des anti GPIIbIIIa ?

Reco ACC 2013

Reco ESC 2012

L’administration précoce d’anti GPIIbIIIa permet-elle d’augmenter le taux d’artère TIMI 3 à l’admission ?

05

101520253035404550

Relax AMI FI NESSE OnTI ME 2 Mistral

Précoce

Retardée*

p=0,01

210 2452 984 256n

* ou placebo

ETUDESRANDOMISEES

ns

ns

ns

L’administration précoce d’anti GPIIbIIIa permet-elle d’augmenter le taux d’artère TIMI 3 à l’admission ?

05

101520253035404550

Ortolani Eurotransfert ORBI

Précoce

Retardée

p=0,006

1124 1066 1242 (629 préH+/613préH-) n

P < 0,0001

REGISTRES

ns

et en cas de fibrinolyse?

- Quel AAP?- Quel anti coagulant?

En conclusion

Que faire, en pratique?

Protocole de prise en charge du SCA ST+ Décembre 2011, CHU RENNES

Prise en charge pré-hospitalière (équipe SMUR) ou service accueil-urgences

Mise en route du traitement anti-thrombotique

Aspirine : Bolus IV de 500 mg IV puis 160 mg / jour per os en phase hospitalièreHéparine : bolus IV d’héparine non fractionnée 60 u/kg

► si Angioplastie primaire

Protocole de prise en charge du SCA ST+ Décembre 2011, CHU RENNES


Etape 3 : Mise en route du traitement anti-thrombotique

Thiénopyridine : deux situations en fonction du risque hémorragique

► si Angioplastie primaire

Dose de charge orale d’Efient (60 mg) puis 10 mg / jour

Age < 75 anspoids ≥ 60 kgAucun antécédent d’accident vasculaire cérébral Pas d’affection évolutive ou récente, ayant été responsable d’un saignement récent, ou associée à un risque hémorragique élevéPas de prescription au long cours de médicaments augmentant le risque hémorragique (AVK, AINS…)Pas d’insuffisance hépatique ou rénale sévère connue

Pas de risque hémorragique

Protocole de prise en charge du SCA ST+


Si risque hémorragique (au moins un des critères sus cités)

Dose de charge orale de Plavix (300 mg) (une dose supplémentaire de 300 mg sera décidée en salle de cathétérisme par l’opérateur), suivie d’une dose de 150 mg / jour en phase hospitalière puis 75 mg/jour à la sortie.

Etape 3 : Mise en route du traitement anti-thrombotique

Décembre 2011, CHU RENNES


En salle de coronarographie ( stratégie angioplastie primaire)

Vérifier que le patient soit bien sous l’association de deux anti agrégants plaquettaires par voie orale

Pas d’anticoagulation curative au décours d’une ATC sauf indication spécifique (FA, thrombus intraVG, désilet en place, CPBIA) ou prescription du coronarographiste (notamment co-prescription de Réopro® avec prescription d’héparine 7 u / kg / h pendant 12 heures).

Prescription de Réopro en salle de coronarographie en cas de risque élevé (évaluation par le coronarographiste sur plusieurs critères : taille de l’infarctus, diabète, risque ischémique, risque hémorragique, composante thrombotique à l’angiographie, no-reflow).

bolus de 0.25 mg / kg, suivi d’une perfusion de 12 heures de 0.125 μg / kg / mn (maximum, 10 μg /mn)



Aspirine : Bolus IV de 500 mg IV puis 160 mg / jour per os en phase hospitalière

Thiénopyridine : Plavix® dose de charge orale de 300 mg suivie d’une dose d’entretien de75 mg / jour

► si fibrinolyse

Enoxaparine (Lovenox®): deux situations en fonction de l’age et de la fonction rénale:

- Patients < 75 ans et Créat < 221 µmoles/l chez l’homme, < 177 µmoles/l chez la femme : bolus IV de 30 mg suivi 15’ plus tard d’une dose SC de 1 mg/ Kg à répéter toutes les 12 heures. Les deux premières doses ne doivent pas dépasser 100 mg.- Patients > 75 ans : pas de bolus IV. Première dose sous cutanée de 0,75 mg/kg avec un maximum de 75 mg (pour les deux premières doses)- Insuffisance rénale sévère (clearance < 30 ml/mn) : une seule dose par 24 heures (ou utilisation de l’héparine non fractionnée).

si HNF bolus IV de 60 u/kg avec un max de 4000 u puis perfusion de 12 u/kg/h pendant 24 à 48 h avec un max de 1000 u/h


Reco ESC 2012

Are there gender differences Are there gender differences in the management and outcome of STEMI? in the management and outcome of STEMI?

Data from ORBI, a prospective Data from ORBI, a prospective registryregistry of of 5000 patients.5000 patients.

Dr Guillaume Leurent, M.D.Dr Guillaume Leurent, M.D.University Hospital of Rennes (France)University Hospital of Rennes (France)

ORBIORBI

BackgroundBackground

It is said that It is said that women have a worst women have a worst prognostic after STEMIprognostic after STEMI

< more co-morbidities< more co-morbidities

< longer management delays < longer management delays

< less aggressive reperfusion < less aggressive reperfusion strategiesstrategies

ORBIORBI

• ORBI: French acronym (ORBI: French acronym (OObservatoire bservatoire RRégional égional BBreton sur l’reton sur l’IInfarctus du myocarde)nfarctus du myocarde)

≈≈ Brittany regional observational study Brittany regional observational study on myocardial infarctionon myocardial infarction

• an exhaustive collection of an exhaustive collection of consecutive patients with consecutive patients with STEMI in all of the 9 interventional STEMI in all of the 9 interventional cardiology units in Brittany regioncardiology units in Brittany region

• 5000 patients since July 20065000 patients since July 2006

ORBIORBI

MethodsMethods

• Comparison of characteristics, Comparison of characteristics, management and outcome in STEMI management and outcome in STEMI patients, according to their genderpatients, according to their gender

• Analysis of the mortality rate after Analysis of the mortality rate after adjustments when considering data adjustments when considering data aboutabout

the patient, the patient, the delays of revascularisation,the delays of revascularisation, various aspect of revascularisationvarious aspect of revascularisation

MenMen 3826 patients (76.5%)3826 patients (76.5%)

WomenWomen1174 patients (23.5%)1174 patients (23.5%)

ORBI population:ORBI population:5000 patients5000 patients

ResultsResults ORBIORBI




Mean age*Mean age*

Hypertension*Hypertension*

Dyslipidemia*Dyslipidemia*

DiabeteDiabete mellitusmellitus

Current smoking*Current smoking*

History of MI*History of MI*

68.8 68.8 ±14±14

54%54%

45%45%

13%13%

26%26%

4%4%

60.8 60.8 ±12±12

36%36%

52%52%

11%11%

41%41%

8%8%*: p<0.0001*: p<0.0001

ORBIORBIResults: Population characteristicsResults: Population characteristics


Onset ofOnset ofsymptomsymptom

11stst call call

44 mn*44 mn*


60 mn*60 mn*


††: p<0.05; *: p<0.05; *: p<0.0001: p<0.0001


11stst call call

ORBIORBIResults: Revascularisation delaysResults: Revascularisation delays



11stst call call

44 mn*44 mn*

AdmissionAdmission


60 mn*60 mn*


††: p<0.05; *: p<0.05; *: p<0.0001: p<0.0001


11stst call call

AdmissionAdmission

125 mn 125 mn ††130 mn 130 mn ††




11stst call call

44 mn*44 mn*

AdmissionAdmission

PCIPCI


60 mn*60 mn*


††: p<0.05; *: p<0.05; *: p<0.0001: p<0.0001


11stst call call

AdmissionAdmission

PCIPCI

40 mn 40 mn ††45 mn 45 mn ††

125 mn 125 mn ††130 mn 130 mn ††





Results: Revascularisation modalitiesResults: Revascularisation modalitiesORBIORBI

Fibrinolysis Fibrinolysis ††

Coronary angiography* Coronary angiography*

Gp 2b3a recept. inhib.*Gp 2b3a recept. inhib.*

Radial access*Radial access*

Primary angioplastyPrimary angioplasty

Thrombo-aspirationThrombo-aspiration

12%12%

95%95%

53%53%

38%38%

70%70%

43%43%

16%16%

98%98%

59%59%

51%51%

72%72%

47%47%

††: p<0.05; *: p<0.05; *: p<0.0001: p<0.0001




Results: Intra hospital outcomeResults: Intra hospital outcomeORBIORBI

High degree AV block*High degree AV block*

Atrial fibrillation* Atrial fibrillation*

Total length of stay (days)*Total length of stay (days)*

LV ejection fraction (%)LV ejection fraction (%)††

Death*Death*

5%5%

7%7%

7.6 ±47.6 ±4

49 ±1049 ±10

9%9%

2%2%

3%3%

6.7 ±46.7 ±4

51 ±1051 ±10

4%4%

††: p<0.05; *: p<0.05; *: p<0.0001: p<0.0001

Results: Adjusted analysis of the Results: Adjusted analysis of the intra hospital mortalityintra hospital mortality ORBI

ORBI

OR 95%OR 95%

Confidence limitConfidence limitp-valuep-value

Model 1: UnadjustedModel 1: Unadjusted2.172.17

[1.68-2.80][1.68-2.80]p<0.0001p<0.0001


ORBI

OR 95%OR 95%



[1.68-2.80][1.68-2.80]p<0.0001p<0.0001

Model 2: Adjusted for data Model 2: Adjusted for data about patientsabout patients: age, diabete : age, diabete

mellitus, hypertension, mellitus, hypertension, smoking, anterior STEMI, and smoking, anterior STEMI, and

3-vessels or left main 3-vessels or left main coronary artery diseasecoronary artery disease

1.351.35

[1.01-1.79][1.01-1.79]p=0.04p=0.04


ORBI

OR 95%OR 95%



[1.68-2.80][1.68-2.80]p<0.0001p<0.0001

Model 2Model 21.351.35

[1.01-1.79][1.01-1.79]p=0.04p=0.04

Model 3: Adjusted for Model 3: Adjusted for model 2 and model 2 and

revascularisation delays:revascularisation delays: onset of symptoms to onset of symptoms to reperfusion therapyreperfusion therapy

1.641.64

[1.16-2.32][1.16-2.32]p=0.004p=0.004


ORBI

OR 95%OR 95%



[1.68-2.80][1.68-2.80]p<0.0001p<0.0001


[1.01-1.79][1.01-1.79]p=0.04p=0.04


[1.16-2.32][1.16-2.32]p=0.004p=0.004

Model 4: Adjusted for Model 4: Adjusted for model 3 and various model 3 and various

aspect of aspect of revascularisationrevascularisation: : coronary coronary angiography, radial access, angiography, radial access,

primary angioplasty, thrombo-primary angioplasty, thrombo-aspiration, GP2b3a, aspiration, GP2b3a,

fibrinolysisfibrinolysis

1.551.55

[1.10-2.19][1.10-2.19]p=0.01p=0.01

• Compared to men, women have:Compared to men, women have:- More co-morbities (older++)More co-morbities (older++)- Longer delays of revascularisationLonger delays of revascularisation- More intra hospital complicationsMore intra hospital complications

• Persistance of this higher mortality Persistance of this higher mortality after after

full adjustmentfull adjustment

a higher intra hospital mortality ratea higher intra hospital mortality rate

DiscussionDiscussion ORBIORBI

• Delay between symptom onset and Delay between symptom onset and 11stst call for medical assistance: 16 call for medical assistance: 16 min. longermin. longer

• Less « aggressive » managementLess « aggressive » management

Awarness campaign among womenAwarness campaign among women

Discussion: What can we do?Discussion: What can we do? ORBIORBI

Awarness campaign among doctorsAwarness campaign among doctorsinvolved in the management of STEMIinvolved in the management of STEMI

• 1STEMI /4 concerns a woman1STEMI /4 concerns a woman

• Higher intra hospital morbi-mortality, Higher intra hospital morbi-mortality, partially due to co-morbidities and partially due to co-morbidities and longer ischemic timelonger ischemic time

• Need to raise awareness among Need to raise awareness among women and cardiological community women and cardiological community to this persistent problem.to this persistent problem.

ConclusionConclusion ORBIORBI

G. Leurent1, I. Coudert2, M. Gilard3, JP. Hacot4, B. Moquet5, P. Druelles6, G. Rouault7, E. Filippi8, A. Rialan9,D. Boulmier1, M. Bedossa1, H. Le Breton1 - Département de Cardiologie et Maladies Vasculaires, CHU de Rennes(1);

SAMU 35(2), Services de cardiologie de Brest(3); Lorient(4); St Brieuc(5); St Laurent, Rennes(6); Quimper(7); Vannes(8); St Malo(9) - FRANCE

Management and outcome of ST-elevation myocardial infarction in octogenarian patients.Data from ORBI, a prospective registry of 5000 patients.

Conclusion: Octogenarian patients and more represent a large part of patient treated for STEMI, with significant differences in their presentation and management, and a higher mortality. This higher mortality rate persists after adjustement for patient characteristics and delais of coronary reperfusion, but it seems that management of revascularisation has no effect on this mortality rate. For further information: [email protected]

Purpose: To determine the actual management of STEMI in octogenarian patients, and to determine the factors responsable of their higher intra hospital mortality rate.

Methods: We analyzed data collected in "ORBI", a 6 years prospective registry of STEMI patients admitted within 24 h of symptoms onset to an interventional cardiology centre of Brittany (France). Main data about management, intra hospital outcome and prescription at discharge were compared between patients older (Group 1) and younger (Group 2) than 80, with an univariate analysis (table 1). Then, we calculated different odds ratios (OR) for intra hospital mortality (group 1 vs group 2): unadjusted, adjusted when considering data about the patient, the delais and various aspect of revascularisation (table 2).

Group 2 (≤ 80 years old)4450 patients (89%)

Onset ofsymptom

1st call

45 mn*

Admission

125 mn*

PCI

40mn†

---Mean age*--------Female*--------Hypertension*--Diabete mellitusCurrent smoking

Fibrinolysis

16%*

Group 1 (> 80 years old)550 patients (11%)

Onset ofsymptom

1st call

65 mn*

Admission

140 mn*

PCI

49mn†

Fibrinolysis

7%*

85±351%68%13%3%

ORBI population:5000 patients

60±1220%37%11%

*42%

†: p<0.05; *: p<0.0001

<0.0001<0.0001183 (4.1% )183 (4.1% )91 (16.5% )91 (16.5% )MortalityMortality

I nitialmanagement

<0,00011822 (46.6% )22 (5.3%)Cardiovascular rehabilitation

<0.00014057 (95.1% )373 (81.3% )Statine

0.12853 (66.9% )290 (63.2% )ACE inhibitor

<0.00013895 (91.3% )394 (85.8% )β blockers

<0.00014086 (95.8% )413 (90.0% )Clopidogrel/Prasugrel

0.0074167(97.7% )439 (95.6% )Aspirine

Prescription at discharge

<0.00016.8±48.2±5Total length of stay (days)

<0.000150.6±1047.2±12LV ejection fraction (%)

<0.0001161 (3.6%)59 (10%)Atrial fibrillation

<0.0001140 (3%)40 (7%)High degree AV block

I ntra-hospitaloutcome

<0.00011874 (42% )163 (33% )Thrombo aspiration*

0.43197 (72% )386 (78% )Primary angioplasty*

<0.00011511 (34% )140 (28% )Radial access*

<0.00014402 (99% )493 (89% )Coronary angiography

<0.00012674 (60% )223 (40% )GP I Ib/ I I I a receptor inhibitors

p-valueGroup 2N=4450

Group 1n=550

Table 1*Percentages are calculatedonly in patients undergoing

coronary angiographyTable 2: Unadjusted and adjusted OR for intra hospital

mortality (group 1 vs group 2) when considering data about the patient, the delais and various aspect of revascularisation

p-valueOR 95%

Confidence limit

2.47 [1.79-3.41]

p<0.0001

p<0.0001

p<0.0001

p<0.0001

2.73 [1.83-4.07]

2.73 [1.85-4.03]

4.64 [3.55-6.08]

Model 4: Adjusted for model 3 and various

aspect of revascularisation:

coronary angiography, radial access, primary angioplasty, thrombo-aspiration, GP2b3a,

fibrinoysis

Model 3: Adjusted for model 2 and

revascularisation delays (onset of

symptoms to reperfusion therapy)

Model 2: Adjusted for data about patients:

gender, diabete mellitus, hypertension, smoking, anterior STEMI, and 3-

vessels or left main coronary artery disease

Model 1: Unadjusted

Documents

Actualités en cardiologie sur les SCA ST+ Guillaume LEURENT, CHU RENNES Parigné, le 23 Mai 2013