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Dual Antiplatelet Therapy in ACS / PCI Current Recommendations and Corresponding Data Bernhard Meier Cardiology University Hospital Bern Switzerland

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Page 1: Dual Antiplatelet Therapy in ACS / PCI - assets.escardio.orgassets.escardio.org/assets/Presentations/OTHER2013/Davos/Day 3/08-Dual-antiplatelet... · Extended dual antiplatelet therapy

Dual Antiplatelet Therapyin

ACS / PCI

Current Recommendations and Corresponding Data

Bernhard Meier

Cardiology

University Hospital Bern

Switzerland

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Page 3: Dual Antiplatelet Therapy in ACS / PCI - assets.escardio.orgassets.escardio.org/assets/Presentations/OTHER2013/Davos/Day 3/08-Dual-antiplatelet... · Extended dual antiplatelet therapy
Page 4: Dual Antiplatelet Therapy in ACS / PCI - assets.escardio.orgassets.escardio.org/assets/Presentations/OTHER2013/Davos/Day 3/08-Dual-antiplatelet... · Extended dual antiplatelet therapy
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3.4

1.4

0.27 0.28

6.2

2.2

0.3 0.29

0

2

4

6

8

Minor Bleeding Major Bleeding Fatal Bleeding Intracranial

Hemorrhage

Single APT DAPT

(%)

Risk of Bleeding With DAPTSerebruany VL et al. Fund Clin Pharmacology 2008;22:315-21

56%

RR=1.56

(1.47-1.66)47%

RR=1.47

(1.36-1.60)

RR=1.10

(0.87-1.40)

RR=1.07

(0.85-1.35)

18 RCTs With 129,314 Patients Comparing

Single versus Dual Antiplatelet Therapy

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Extended dual antiplatelet therapy after PCI with DESa meta-analysis of randomized trials

Cassese S, Kastrati A, EHJ 2013

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Discontinuation of long term clopidogrel therapy induces platelet rebound hyperaggregability between 2 and 6 weeks post cessation.

(Diehl P, Clinical Research in Cardiology, April 2011)

Clopidogrel Cessation

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(P2Y12)

Thrombin receptor blockers- Direct thrombin inhibitors

- heparin- low molecular weight heparin- bivalirudin (po)- dabigatran (po)

- Xa inhibitors- rivaroxaban- apixaban

Cangrelor (iv)

Elinogrel (po/iv)

Ticagrelor

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Brilique®

Efient®

Plavix®

Oral Antiplatelet Agents(via receptor P2Y12)

Schömig A

NEJM 361;11;1108-11

(Triazolo-Pyrimidine) (Thienopyridine) (Thienopyridine)

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TRITON-TIMI 38: Landmark Analysis for Primary Efficacy Endpoint

• Hazard ratios based on Kaplan-Meier estimates; HR = Hazard ratio

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

0

2

4

6

0 1 2 3 3 30 90 180 270 360 450

HR 0.82 (0.71 -

0.96)

p = 0.01

5.6

4.7

Days after Randomization

8

Days after Randomization

Pri

mary

En

dp

oin

t (%

)

HR 0.80 (0.70 -

0.93)

p = 0.003

6.9

5.6

Prasugrel

Clopidogrel

Prasugrel

Clopidogrel

Cardiovascular Death, Nonfatal Myocardial Infarction, Nonfatal Stroke

20 % RRR18 % RRR

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Mortality benefit in TRITON

2,6

4,3 4,2

1,6

3,3 3,4

0

1

2

3

4

5

30 days 15 month Diabetes

Clopidogrel

Prasugrel

- 26 %,

p=0.129

STEMI

-15 %,

p=0.40

- 38 %,

p=0.044

CV-death

Montalescot et al, 2009 Lancet 373

Wiviott et al. 2008 Circulation 118

n = 3534n = 3146

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Early and Late Risks of Prasugrel Over Clopidogrel in ACS Patients Undergoing PCI

Antman E et al. J Am Coll Cardiol 2008;51:2028-33

Major Bleeding

0-3 Days 3-450 Days

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Stent Thrombosis (ARC Definite + Probable)

0

1

2

3

0 30 60 90 180 270 360 450

HR 0.48

P <0.0001

Prasugrel

Clopidogrel2.4

(142)

NNT= 77

1.1

(68)

Days

En

dp

oin

t (%

)

Any Stent at Index PCI

N= 12,844

Triton-TIMI 38 – Prasugrel vs. ClopidogrelWiviott SD et al. N Engl J Med 2007;357:2001-15

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Coronary

Stent ThrombosisBefore DES Introduction

Togni M, Windecker S,

Meier B

Curr Interv Cardiol Rep

3: 306-310, 2001

..... in particular, the risk of late

stent thrombosis driven by

inhibitory effects on

endothelial regrowth, or late

toxic effects on vascular cells,

may be encountered with

stent-based drug delivery .....

Wenaweser P, EHJ 2005;26:1180-7

Wenaweser P, JACC 2008;52:1134-40

BMS

DES

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??

??

Bleeds

Ischemic

Events

Development of Oral Anti-Platelet Therapy

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Vorapaxar (Thrombin-Receptor (PAR-1) Antagonist) in ACS (TRACER)

Tricoci P, N Engl J Med 2012;366:20-33Merck (MSD)

• Death (cardiovascular)• MI• Stroke

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Vorapaxar (Thrombin-Receptor (PAR-1) Antagonist) in ACS (TRACER)

Tricoci P, N Engl J Med 2012;366:20-33

TIMI Bleeding

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Moser M, Bode C, European Heart Journal (2011) 32, 2734–2735

ACS / AF and New Oral Anticoagulants

* Clinical benefit

# Stopped for bleeding

## Stopped for superiority over ASA

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Local Guidelines for Antiplatelet Therapy in ACS patients

ST-elevation MIPeri-Procedural

Post-Procedural

ASA 250-500 mg iv

Prasugrel 60 mg loading dose irrespective of preloading with

clopidogrel

Prasugrel 10 mg* for ≥1 year

ASA indefinitely

Non ST-elevation MI

Peri-Procedural

Post-Procedural

(or severe (un)stable CAD)

ASA 250-500 mg iv

Clopidogrel 600 mg or prasugrel 60 mg or ticagrelor 180 mg

loading dose

Clopidogrel 75 mg 2x1 for 1 week

followed by 75 mg for ≥1 year

or

Prasugrel 10 mg* for ≥1 year

or

Ticagrelor 90 mg 2x1 for ≥1 year

ASA indefinitely

*5mg in patients with age >75 years or weight <60kg

Contraindication: history of stroke (to be rediscussed)

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Trial Design

NON-STEMI / Troponin +, n=4100+

(Clopidogrel naïve or long term 75mg)

Transfer for planned PCI (>2h and <24h)

Randomize

Upstream

+

Transfer

to PCI

(>2h to <24h)

Placebo Prasugrel 30

CathlabPCI

CAG

Prasugrel 60 Prasugrel 30

All:

MD P 10

for 30d30d FU

PCI

CAG

PE: CV-D, MI, Stroke, uTVR, GPI bailout @7d

SE: All TIMI major bleeding @7; NetClinOutcome@30d

Stopped prematurely because of pre PCI bleedings