Prasugrel compared with clopidogrel in patients undergoing percutaneous coronary intervention for ST-elevation myocardial infarction (TRITON-TIMI 38): double-blind, randomised controlled trial.
BACKGROUND
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.


METHODS
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. The primary endpoint 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. This trial is registered with ClinicalTrials.gov, number NCT00097591.


RESULTS
At 30 days, 115 (6.5%) individuals assigned prasugrel had met the primary endpoint compared with 166 (9.5%) allocated clopidogrel (hazard ratio 0.68 [95% CI 0.54-0.87]; p=0.0017). This effect continued to 15 months (174 [10.0%] vs 216 [12.4%]; 0.79 [0.65-0.97]; p=0.0221). The key secondary endpoint of cardiovascular death, myocardial infarction, or urgent target vessel revascularisation was also significantly reduced with prasugrel at 30 days (0.75 [0.59-0.96]; p=0.0205) and 15 months (0.79 [0.65-0.97]; p=0.0250), as was stent thrombosis. Treatments did not differ with respect to thrombolysis in myocardial infarction (TIMI) major bleeding unrelated to coronary-artery bypass graft (CABG) surgery at 30 days (p=0.3359) and 15 months (p=0.6451). TIMI life-threatening bleeding and TIMI major or minor bleeding were also similar with the two treatments, and only TIMI major bleeding after CABG surgery was significantly increased with prasugrel (p=0.0033).


CONCLUSIONS
In patients with STEMI undergoing PCI, prasugrel is more effective than clopidogrel for prevention of ischaemic events, without an apparent excess in bleeding.
Montalescot
Gilles
G
Institute of Cardiology, INSERM U856, Université Paris 6, Pitié-Salpêtrière Hospital (AP-HP), Paris, France.
Wiviott
Stephen D
SD
Braunwald
Eugene
E
Murphy
Sabina A
SA
Gibson
C Michael
CM
McCabe
Carolyn H
CH
Antman
Elliott M
EM
D000368:Aged; D015906:Angioplasty, Balloon, Coronary; D001241:Aspirin / Q000009:adverse effects / Q000627:therapeutic use; D000077144:Clopidogrel; D001026:Coronary Artery Bypass; D004311:Double-Blind Method; D023381:Endpoint Determination; D005260:Female; D006470:Hemorrhage / Q000139:chemically induced; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000628:therapy*; D010879:Piperazines / Q000009:adverse effects / Q000627:therapeutic use*; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D000068799:Prasugrel Hydrochloride; D013876:Thiophenes / Q000009:adverse effects / Q000627:therapeutic use*; D013988:Ticlopidine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use
D010879:Piperazines; D010975:Platelet Aggregation Inhibitors; D013876:Thiophenes; D000077144:Clopidogrel; D000068799:Prasugrel Hydrochloride; D013988:Ticlopidine; D001241:Aspirin