Dual Antiplatelet Therapyin
ACS / PCI
Current Recommendations and Corresponding Data
Bernhard Meier
Cardiology
University Hospital Bern
Switzerland
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
Extended dual antiplatelet therapy after PCI with DESa meta-analysis of randomized trials
Cassese S, Kastrati A, EHJ 2013
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
(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
Brilique®
Efient®
Plavix®
Oral Antiplatelet Agents(via receptor P2Y12)
Schömig A
NEJM 361;11;1108-11
(Triazolo-Pyrimidine) (Thienopyridine) (Thienopyridine)
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
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
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
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
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
??
??
Bleeds
Ischemic
Events
Development of Oral Anti-Platelet Therapy
Vorapaxar (Thrombin-Receptor (PAR-1) Antagonist) in ACS (TRACER)
Tricoci P, N Engl J Med 2012;366:20-33Merck (MSD)
• Death (cardiovascular)• MI• Stroke
Vorapaxar (Thrombin-Receptor (PAR-1) Antagonist) in ACS (TRACER)
Tricoci P, N Engl J Med 2012;366:20-33
TIMI Bleeding
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
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)
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