BACKGROUND—Elderly patients are at elevated risk of both ischemic and bleeding complications after an acute coronary syndrome (ACS), and display higher on-clopidogrel platelet reactivity as compared to younger patients. Prasugrel 5 mg provides more predictable platelet inhibition, as compared to clopidogrel, in the elderly, suggesting the possibility of reducing ischemic events without increasing bleeding. METHODS—In a multicenter, randomized, open-label, blinded-endpoint trial, we compared a once daily maintenance dose of prasugrel 5 mg with the standard clopidogrel 75 mg in patients >74 years with ACS undergoing percutaneous coronary intervention (PCI). The primary endpoint was the composite of mortality, myocardial infarction, disabling stroke and re-hospitalization for cardiovascular causes or bleeding within one year. The study was designed to demonstrate superiority of prasugrel 5 mg over clopidogrel 75 mg. RESULTS—Enrolment was interrupted, according to pre-specified criteria, after a planned interim analysis, when 1443 patients (40% women, mean age 80 years) had been enrolled, with a median follow-up of 12 months, due to futility for efficacy. The primary endpoint occurred in 121 patients (17%) with prasugrel and 121 (16.6%) with clopidogrel (HR 1.007, 95% CI, 0.78-1.30; P =0.955). Definite/probable stent thrombosis rates were 0.7% with prasugrel vs 1.9% with clopidogrel (OR 0.36, C.I. 0.13-1.00, p=0.06). Bleeding Academic Research Consortium types ≥2 were 4.1% with prasugrel vs 2.7% with clopidogrel (OR 1.52, C.I. 0.85-3.16, P= 0.18). CONCLUSIONS—The present study in elderly ACS patients showed no difference in the primary endpoint between reduced-dose prasugrel and standard-dose clopidogrel. However, the study should be interpreted in the light of premature termination of the trial. CLINICAL TRIAL REGISTRATION—URLhttps://clinicaltrials.gov/ Unique IdentifierNCT01777503