Safety and efficacy of prasugrel compared with clopidogrel in different regions of the world.

Background: Among patients with acute coronary syndrome (ACS), demographics, procedural characteristics and adjunctive medications differ globally. We examined whether there were differential effects of prasugrel compared with clopidogrel in the multinational TRITON-TIMI 38 study.

Methods: We divided the enrollment into 5 pre-specified geographic regions. Patients were randomized to prasugrel or clopidogrel without regard to country of enrollment. End points are expressed as Kaplan-Meier failure estimates through 15 months. Heterogeneity was evaluated using Cox proportional hazards model. Additional sensitivity analyses were performed by dividing countries into categories based on the Human Development Index (HDI), which is a composite measure of social and economic development.

Results: 13,608 patients were enrolled. Clinical characteristics including age, comorbidities, ACS presentation, stent types, and adjunctive medications differed broadly among regions. Despite these differences, no regional heterogeneity was observed with prasugrel compared to clopidogrel in the reduction of ischemic events (HR range: 0.76-0.87, p(interaction)>0.10 for each) and stent thrombosis (HR range: 0.34-0.72, p(interaction)>0.10 for each) or in the increased rate of non-CABG TIMI major bleeding (HR range: 1.16-1.76, p(interaction)>0.10 for each). There was a consistent trend in net clinical benefit (all cause death/MI/stroke/non-CABG TIMI major bleeding) favoring prasugrel (HR range: 0.81-0.97, p(interaction)>0.10 for each). Consistent results were also observed regarding the safety and efficacy of prasugrel compared with clopidogrel in both developed and developing countries.

Conclusions: Despite differences in patient demographics, procedural techniques and adjunctive medications, consistent reduction in ischemic events and increased bleeding were seen with prasugrel compared with clopidogrel throughout the world.