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. Findings 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). Interpretation In patients with STEMI undergoing PCI, prasugrel is more effective than clopidogrel for prevention of ischaemic events, without an apparent excess in bleeding. Funding Daiichi Sankyo and Eli Lilly.