Balancing efficacy and safety in the TRITON-TIMI 38 trial

Abstract

The TRITON-TIMI 38 study tested the hypothesis that prasugrel compared with clopidogrel is more efficacious in prevention of ischaemic events in patients undergoing percutaneous coronary intervention (PCI) for either ST-elevation myocardial infarction or for non-ST-elevation acute coronary syndromes. In a double-blind design, 13 608 patients were randomly assigned to receive prasugrel or clopidogrel. During 15-month follow-up, prasugrel compared with clopidogrel significantly reduced the incidence of the primary endpoint, the composite of the rate of cardiovascular death, myocardial infarction, or stroke from 12.1 to 9.9% (hazard ratio: 0.81; P < 0.001). Significant benefit of prasugrel was found during the first 3 days (hazard ratio: 0.82; P = 0.01) and from day 4 to the end of the study (hazard ratio: 0.8; P = 0.003). Of the patients treated with prasugrel, 2.4% experienced at least one TIMI major haemorrhage unrelated to coronary artery bypass graft, compared with 1.8% treated with clopidogrel (hazard ratio: 1.32; P = 0.03). Thus, in the entire study group, the balance of efficacy and safety was in favour of prasugrel with an absolute 2.2% reduction in the primary efficacy endpoint by prasugrel when compared with clopidogrel that was opposed by an only 0.6% increase in major haemorrhage. In conclusion, in patients with acute coronary syndromes undergoing PCI prasugrel significantly reduced the incidence of ischaemic events, both in the acute and long term. Prasugrel was associated with an increased risk of bleeding. In the entire cohort, the superior efficacy of prasugrel outweighed the increased risk of bleeding.