A Comparison of Reduced-Dose Prasugrel and Standard-Dose Clopidogrel in Elderly Patients with Acute Coronary Syndromes Undergoing Early Percutaneous Revascularization

Background: Elderly patients are at elevated risk of both ischemic and bleeding complications after an acute coronary syndromeand display higher on- clopidogrelplatelet reactivity compared with younger patients. Prasugrel5 mg provides more predictable platelet inhibition compared with clopidogrelin the elderly, suggesting the possibility of reducing ischemic events without increasing bleeding. Methods: In a multicenter, randomized, open-label, blinded end point trial, we compared a once-daily maintenance doseof prasugrel5 mg with the standard clopidogrel75 mg in patients >74 years of age with acute coronary syndromeundergoing percutaneous coronary intervention. The primary end point was the composite of mortality, myocardial infarction, disabling stroke, and rehospitalization for cardiovascular causes or bleeding within 1 year. The study was designed to demonstrate superiority of prasugrel5 mg over clopidogrel75 mg. Results: Enrollment was interrupted, according to prespecified 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, because of futility for efficacy. The primary end point occurred in 121 patients (17%) with prasugreland 121 (16.6%) with clopidogrel(hazard ratio, 1.007; 95% confidence interval, 0.78–1.30; P =0.955). Definite/probable stent thrombosis rates were 0.7% with prasugrelversus 1.9% with clopidogrel(odds ratio, 0.36; 95% confidence interval, 0.13–1.00; P =0.06). Bleeding Academic Research Consortium types 2 and greater rates were 4.1% with prasugrelversus 2.7% with clopidogrel(odds ratio, 1.52; 95% confidence interval, 0.85–3.16; P =0.18). Conclusions: The present study in elderly patients with acute coronary syndromesshowed no difference in the primary end point between reduced-dose prasugreland standard-dose clopidogrel. However, the study should be interpreted in light of the premature termination of the trial. Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01777503.