Antithrombotische Therapie bei ACS: Müssen

wir etwas ändern?

Prof. Dr. med. Dirk Sibbing

20. Oktober 2018

• Research grants: Roche Diagnostics, Daiichi Sankyo

• Speaker fees / Advisory board activities: Sanofi, Bayer,

Astra Zeneca, Pfizer, Daiichi Sankyo, Haemonetics, BMS

COI

20 Jahre DAPT Studien

35 Studien

>225,000

Patienten

ESC DAPT Guidelines, Valgimigli et al., EHJ 2017

2018 ESC Guidelines: Antithrombotika

BivalirudinDabigatranEnoxaparin UFH

ApixabanEdoxaban

Rivaroxaban

VKAs

Factor Xa

Thrombin

Fibrin

FibrinoganProthrombinCoagulation

cascadeTissu Factor

(Tissue lesion)

An

ticoagu

lant d

rug

Aspirin

DAPT

ClopidogrelPrasugrelTicagrelorCangrelor

An

tiplatelet d

rug

GPIIb/IIIaactivation

TxA2

ADP

GPIIb/IIIa Inhibitors(Abciximab,Eptifibatide,

Tirofiban)

Glycoprotein IIb/IIIa receptor

Soluble mediators (ADP, TxA2)

Clot-bound thrombin/FXa

2018 ESC/EACTS guidelines on myocardial revascularization, EHJ 2018

Agenda

1) Was sind die aktuellen Empfehlungen

zur dualen Plättchenhemmung bei ACS

Patienten ?

2) Strategien zur Individualisierung der

Plättchenhemmung in 2018: Länger?

Kürzer? De-Eskalation?

Agenda

1) Was sind die aktuellen Empfehlungen

zur dualen Plättchenhemmung bei ACS

Patienten ?

2) Strategien zur Individualisierung der

Plättchenhemmung in 2018: Länger?

Kürzer? De-Eskalation?

2018 ESC Guidelines

2018 ESC/EACTS Guidelines on myocardial revascularisationEuropean Heart Journal (2018) 00, 1-96 - doi:10.1093/eurheartj/ehy394

www.escardio.org/guidelineswww.escardio.org/guidelines

2018 ESC/EACTS Guidelines on myocardial revascularization

2

Authors/Task Force Members: Franz-Josef Neumann (ESC Chairperson) (Germany),Miguel Sousa-Uva (EACTS Chairperson) (Portugal), Anders Ahlsson (Sweden),Fernando Alfonso (Spain), Adrian P. Banning (UK), Umberto Benedetto (UK),Robert A. Byrne (Germany), Jean-Philippe Collet (France), Volkmar Falk (Germany),Stuart J. Head (The Netherlands), Peter Jüni (Canada), Adnan Kastrati (Germany),Akos Koller (Hungary), Steen D. Kristensen (Denmark), Josef Niebauer (Austria),Dimitrios J. Richter (Greece), Petar M. Seferovic (Serbia), Dirk Sibbing (Germany),Giulio G. Stefanini (Italy), Stephan Windecker (Switzerland), Rashmi Yadav (UK),Michael O. Zembala (Poland).

The Task Force on myocardial revascularization of the European Society of Cardiology (ESC)and European Association for Cardio-Thoracic Surgery (EACTS).

Developed with the special contribution of the European Association for Percutaneous Cardiovascular Interventions (EAPCI).

Aktuelle ESC 2018 Leitlinie

Recommendations Class Level

Pre-treatment and antiplatelet therapy

Aspirin is recommended for all patients without contraindications at an

initial oral loading dose of 150-300 mg (or 75-250 mg i.v.), and at a

maintenance dose of 75-100 mg daily long-term.

I A

A P2Y12 inhibitor is recommended in addition to aspirin, maintained over

12 months unless there are contraindications such as an excessive risk

of bleeding. Options are:

I A

• Prasugrel in P2Y12-inhibitor naïve patients who proceed to PCI

(60 mg loading dose, 10 mg daily dose). I B

• Ticagrelor irrespective of the preceding P2Y12 inhibitor regimen

(180 mg loading dose, 90 mg b.i.d.). I B

2018 ESC/EACTS guidelines on myocardial revascularization, EHJ 2018

• Clopidogrel (600 mg loading dose, 75 mg daily dose) only when prasugrel or ticagrelor are not available or are contraindicated.

I B

DAPT Dauer: NSTEMI

2018 ESC/EACTS guidelines on myocardial revascularization, EHJ 2018

Antithrombotic Treatment in Patients Undergoing Percutaneous Coronary Intervention

NSTE-ACSTreatment Indication

(Pre-) Treatment DAPT

Time

1 month

3 months

6 months

12 months

30 months

36 months

DA

PT

Du

rati

on

A T C

High Bleeding Risk

No Yes

12 months DAPT

A C

A P

A Tor

or

A T

A P A C

or

DAPT >12 months

A T

orA C

6 months DAPT A

T

C

P

Antiplatelet drugs :

Aspirin

Clopidogrel

Prasugrel

Ticagrelor

DAPT Dauer: STEMI

2018 ESC/EACTS guidelines on myocardial revascularization, EHJ 2018

Antithrombotic Treatment in Patients Undergoing Percutaneous Coronary Intervention

STEMITreatment Indication

(Pre-) Treatment DAPT

Time

1 month

3 months

6 months

12 months

30 months

36 months

DA

PT

Du

rati

on

A T P C

No Yes

12 months DAPT

A C

A P

A Tor

or

A T

A P A C

or

DAPT >12 months

A T

orA C

6 months DAPT

High Bleeding Risk

A

T

C

P

Antiplatelet drugs :

Aspirin

Clopidogrel

Prasugrel

Ticagrelor

Triple: Was? Wielange?

2018 ESC/EACTS guidelines on myocardial revascularization, EHJ 2018

NOACs & Triple

2018 ESC/EACTS Guidelines on myocardial revascularisationEuropean Heart Journal (2018) 00, 1-96 - doi:10.1093/eurheartj/ehy394

www.escardio.org/guidelineswww.escardio.org/guidelines

Dual antiplatelet therapy duration in patients with indication for oral anticoagulation

20

Recommendations Class Level

Dual therapy with clopidogrel 75 mg/day and an OAC should be considered as an alternative to 1-month triple antithrombotic therapy in patients in whom the bleeding risk outweighs the ischaemic risk.

IIa A

In patients with non-valvular AF requiring anticoagulation and antiplatelet treatment, a NOAC should be preferred over VKAs. IIa A

In patients with an indication for a VKA in combination with aspirin and/or clopidogrel, the dose intensity of the VKA should be care-fully regulated with a target INR in the lower part of the re-commended target range and time in the therapeutic range >65%.

IIa B

Discontinuation of antiplatelet treatment in patients treated withOAC should be considered at 12 months. IIa B

NEW:

PIONNER

RE-DUAL

Agenda

1) Was sind die aktuellen Empfehlungen

zur dualen Plättchenhemmung bei ACS

Patienten ?

2) Strategien zur Individualisierung der

Plättchenhemmung in 2018: Länger?

Kürzer? De-Eskalation?

Scores

2017 ESC/EACTS DAPT Guidelines, EHJ 2017

DAPT Eskalation

• GRAVITAS

• TRIGGER-PCI

• ARCTIC

Kein Benefit einer „Guided* Eskalation“

Price et al., JAMA 2011, Trenk et al., JACC 2012, Collet et al., NEJM 2012

*Guided = gesteuert durch Plättchenfunktionstestung

Prasugrel: Ischämien vs.

Blutungen

Antman et al., JACC 2009, Wiviott et al., NEJM 2007

Akute Phase Chronische Phase

Defi

nit

e S

T

Becker et al., EHJ 2011; Velders et al., Heart 2016

Ticagrelor: Ischämien vs.

Blutungen

PLATO

Real-World Daten zu DAPT De-Eskalation (Switching)

15 % 28 % DAPT De-Eskalation

Zettler et al., AHJ 2017

Cuisset et al., EHJ 2017

PR

O

TOPIC Studie

De Luca et al., Eurointervention 2017

CO

NT

RA

SCOPE Register

Clopidogrel: Wirkung & Outcome

Gurbel et al., Circulation 2003 Aradi, …, Sibbing, EHJ 2015

Plattchenfunktionstestung (PFT) als “Tool” um eine DAPT De-Eskalation

sicherer zu machen

20,839 Patienten

Patienten & Studienarme

Biomarker

positive ACS

patients

(n=2610) with

successful

PCI

7 days

clopidogrel

7 days

prasugrel

14 days prasugrel

11 ½ months

prasugrel

11 ½ months

clopidogrel

PF

T (

Mu

ltip

late

an

aly

ser)

@ 2

weeks a

fter

dis

ch

arg

e

Low

Responders

(40%)

Good

Responders

(60%)

Follow-up:

Guided de-escalation

(n=1304)

11 ½ months

prasugrel

Ho

sp

ita

l d

isc

ha

rge

Control

(n=1306)

98%

@ 2 weeks

96%

@ 12 months

Dec 2013 –

May 2016

R*

1:1

unchanged

therapy

Ad

he

ren

ce

to

tre

atm

en

t:

>9

4%

in

bo

th g

rou

ps

Sibbing et al., Lancet 2017

Primärer Studienendpunkt

0

2

4

6

8

10

0 60 120 180 240 300 360 (days)

HR 0·81 (0·62-1·06)

p=0·0004 for non-inferiority

(p=0·1202 for superiority)

(CVD, MI, stroke, BARC ≥2)

-- Control group

-- Guided de-escalation group

No. at risk Control

De-escalation 1306

1304

1238

1234

1220

1213 1190

1189

1132

1129 1124

1124

924

942

9·0%

7·3%

Eve

nt p

rob

ab

ility

(%

)

Sibbing et al., Lancet 2017

Blutungen (BARC 1-5)

Sekundäre Studienendpunkt

(CV

D,

MI, s

troke

)

Ischämien

Sibbing et al., Lancet 2017

PEGASUS: Primärer

Endpunkt

Bonaca et al., NEJM 2015

ARR: 1.2% RRR: 15% NNT: 84

PEGASUS: Blutungen

Bonaca et al., NEJM 2015

PEGASUS: Mehrgefäß-KHK

Bansilal et al., JACC 2018

DAPT Alternativen in 2018

2018 ESC/EACTS guidelines on myocardial revascularization, EHJ 2018

Recommendations Clas

s Leve

l

De-escalation of P2Y12 inhibitor treatment (e.g. with a switch from prasugrel or ticagrelor to clopidogrel) guided by platelet function testing may be considered as an alternative DAPT strategy, especially for ACS patients deemed unsuitable for 12-month potent platelet inhibition.

IIb B

In patients with ACS who have tolerated DAPT without a bleeding complication, continuation of DAPT for longer than 12 months may be considered.

IIb A

∑: Alternative DAPT Strategien zur DAPT Eskalation und De-eskalation

PEGASUS DAPT

TROPICAL-ACS TOPIC

Zusammenfassung

• Standards zur Plättchenhemmung nach ESC Leitlinie sind eine 12 monatige DAPT Dauer mit ASS + Prasugrel oder Ticagrelor und eine 6 monatige DAPT Dauer bei hohem Blutungsrisiko

• Alternative Strategien und DAPT Optionen sind

a) eine verlängerte DAPT Dauer mit potenten Plättchenhemmern wenn das Ischämierisiko überwiegt

b) sowie eine verkürzte DAPT Dauer oder eine DAPT De-Eskalation bei hohem Blutungsrisiko oder aus sozio-ökonomischer Indikation

• Aktuelle Leitlinien unterstützen eine individualisierte Therapie in

ausgewählten Fällen und insb. i.R. einer DAPT De-Eskalation

Vielen Dank für die

Aufmerksamkeit!