Articles www.thelancet.com Vol 373 February 28, 2009 723 Prasugrel compared with clopidogrel in patients undergoing percutaneous coronary intervention for ST-elevation myocardial infarction (TRITON-TIMI 38): double-blind, randomised controlled trial Gilles Montalescot, Stephen D Wiviott, Eugene Braunwald, Sabina A Murphy, C Michael Gibson, Carolyn H McCabe, Elliott M Antman, for the TRITON-TIMI 38 investigators Summary 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. Introduction Major innovations in catheter-based management of ST-segment elevation myocardial infarction (STEMI) include use of bare metal and drug-eluting stents and platelet glycoprotein IIb/IIIa inhibitors. Use of drug-eluting stents has significantly lowered restenosis but has had little effect on ischaemic events such as death, reinfarction, or stent thrombosis. 1–3 Conversely, glycoprotein IIb/IIIa inhibitors have had no effect on restenosis but have been associated with a reduction in major ischaemic events associated with percutaneous coronary intervention (PCI) in patients with STEMI. 4 As use of stents has grown, thienopyridines—especially clopidogrel—have become increasingly important for treatment of STEMI. 5–10 However, up to now, no randomised controlled trials have been undertaken to compare clopidogrel (or the first-generation thienopyridine, ticlopidine) with placebo in patients undergoing PCI for STEMI. The effectiveness of clopidogrel in this setting has been presumed on the basis of results of studies of scheduled PCI. 11–13 Prasugrel is a novel third-generation thienopyridine and a more potent blocker of the platelet P2Y 12 receptor than clopidogrel, producing consistent platelet inhibi- tion. 14 The TRial to assess Improvement in Therapeutic Outcomes by optimizing platelet inhibitioN with prasugrel–Thrombolysis In Myocardial Infarction (TRITON-TIMI) 38 was designed to compare clopi- dogrel with prasugrel. In a previous report, prasugrel was superior to clopidogrel in reduction of ischaemic events in patients undergoing PCI for the entire spectrum of acute coronary syndrome, albeit with increased bleeding. 15 We report here results for the STEMI population, which represents the first large experience for prasugrel in mechanical reperfusion of STEMI. Lancet 2009; 373: 723–31 See Comment page 695 Institute of Cardiology, INSERM U856, Université Paris 6, Pitié-Salpêtrière Hospital (AP-HP), Paris, France (Prof G Montalescot MD); and TIMI Study Group, Cardiovascular Division, Department of Medicine, Brigham and Women’s Hospital, Boston, MA, USA (S D Wiviott MD, E Braunwald MD, S A Murphy MPH, C M Gibson MD, C H McCabe BS, E M Antman MD) Correspondence to: Prof Gilles Montalescot, Bureau 236, Institute of Cardiology, INSERM U856, Pitié-Salpêtrière Hospital (AP-HP), 47 Boul de l’Hôpital, 75013 Paris, France gilles.montalescot@psl.aphp.fr