Prof Gilles Montalescot MD a , Stephen D Wiviott MD b, Eugene Braunwald MD b, Sabina A Murphy MPH b, C Michael GibsonMD b, Carolyn H

McCabe BS b, Elliott M Antman MD b, for the TRITON-TIMI 38 investigators The Lancet, Volume 373, Issue 9665, Pages 723 - 731, 28 February 2009

Mechanical reperfusion with stenting for ST-elevation myocardial infarction (STEMI) is supported by dual antiplatelet treatment with aspirin and clopidogrel.

Prasugrel, a potent and rapid-acting thienopyridine, is a potential alternative to clopidogrel.

We aimed to assess prasugrel versus clopidogrel in patients undergoing percutaneous coronary intervention (PCI) for STEMI.

We undertook a double-blind, randomised controlled trial in 707 sites in 30 countries.

3534 participants presenting with STEMI were randomly assigned by interactive voice response system either prasugrel (60 mg loading, 10 mg maintenance [n=1769]) or clopidogrel (300 mg loading, 75 mg maintenance [n=1765]) and were unaware of the allocation.

was cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke. Efficacy analyses were by intention to treat. Follow-up was to 15 months, with secondary analyses at 30 days. 

All ACS/PCI patientsN=13608

UA/NSTEMI patients

N=10074

STEMI patientsN=3534

Primary PCIN=2438 (69%)

Secondary PCI

N=1094 (31%)*

ClopidogrClopidogrelel

N=1235N=1235

PrasugrelPrasugrelN=1203N=1203

ClopidogrClopidogrelel

N=530N=530

PrasugrelPrasugrelN=564N=564

Montalescot et al. The lancet 2009

* 2 patients were missing data for primary or secondary

TRITON-TIMI 38TRITON-TIMI 38

TRITON allowed recruitment of STEMI patients undergoing primary PCI when they presented < 12

hours of symptom onset or secondary PCI when they presented late

0

1

2

3

4

5

6

TIMI majorbleed

Lifethreatening

TIMI majoror minor

clopidogrel

prasugrel

P=0.03P=0.03

P=0.01P=0.01

P=0.002P=0.002

Wiviott et al.Wiviott et al. New Engl J Med New Engl J Med 2007;357:2001-20152007;357:2001-2015

0

5

10

15

0 30 60 90 180 270 360 450

HR 0.81(0.73-0.90)

Days

CV

Death

, M

I, S

troke (%

)

12.1

9.9

NNT= 46

Prasugrel

Clopidogrel

P<0.001

Montalescot et al.

Variable Primary PCI(%)

Secondary PCI(%)

p

Age (years) 59 58 0.01

History of diabetes 16.8 24.1 0.001

Prior CABG 1.9 3.2 0.02

Multivessel PCI 6.5 11.0 0.001

GPIIb/IIIa inhibitor 64.5 59.8 0.01

Creatinine clear. < 60mL/min 11.4 8.8 0.02

was cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke.

Efficacy analyses were by intention to treat.

Follow-up was to 15 months, with secondary analyses at 30 days.

End point  Clopidogrel(%) 

Prasugrel(%)  Hazard ratio (95% CI) 

Cardiovascular death, nonfatal MI, and nonfatal stroke 

9.5 6.5 0.68 (0.54-0.87)

Cardiovascular death, nonfatal MI, and TVR 

8.8 6.7 0.75 (0.59-0.96)

Cardiovascular death and MI 

8.8 6.2 0.70 (0.55-0.90)

Cardiovascular death 

2.4 1.4 0.61 (0.37-1.00)

End pointMI 

(CLOPIDOGREL)7.0

(PRASUGREL)4.9

0.70 (0.53-0.92)

TLR  1.9 1.3 0.66 (0.39-1.14)

Stroke  0.9 0.4 0.43 (0.18-1.06)

Stent thrombosis 

2.4 1.2 0.49 (0.28-0.84)

TIMI major bleeding unrelated to CABG surgery 

1.3 1.0 0.74 (0.39-1.38)

End point  Clopidogrel(%) 

Prasugrel(%)  Hazard ratio (95% CI) 

Cardiovascular death, nonfatal MI, and nonfatal stroke 

12.4 10.0 0.79 (0.65-0.97)

Cardiovascular death, nonfatal MI, and TVR 

12.0 9.6 0.79 (0.65-0.97) 

Cardiovascular death and MI 

11.5 8.8 0.75 (0.61-0.93)

Cardiovascular death 

3.4 2.4 0.74 (0.50-1.09)

Montalescot et al.

14.6 14.7

12.2 12.5

0

2

4

6

8

10

12

14

16

18 p=0.02NNT=42

Death / non-fatal MI /non-fatal stroke or

major non-CABG bleeding

Death / MI /stroke/major bleeding

(CABG and non-CABG)

p=0.04NNT=45

Clopidogrel

Prasugrel

Pro

port

ion

of

pop

ula

tion

(%

)

Montalescot

Prasugrel was superior to standard dose clopidogrel to prevent ischaemic events

Prasugrel did not have more bleeding events compared to those who were treated with clopidogrel, and this was equally true for:◦ Primary PCI◦ Secondary PCI◦ Major bleeding◦ Minor bleeding

These data make prasugrel an especially attractive alternative to clopidogrel in PCI for STEMI

In his editorial, Stone notes several limitations of the TRITON study, the first being the dose of the comparator drug.

In the study, prasugrel was compared with a 300-mg loading dose of clopidogrel rather than the more potent 600-mg dose, the current standard of care for primary PCI. 

He also notes that STEMI patients enrolled in the study between 12 hours and 14 days after symptom onset, designated secondary PCI, likely did not receive the full benefit of clopidogrel because of inadequate preloading.

Overall, 72% of patients in the clopidogrel arm received the study drug during PCI, whereas just 27% were preloaded within the allocated 24 hours prior to the procedure.