|| Checking for direct PDF access through Ovid
The novel thienopyridine prasugrel has been shown to reduce platelet aggregation in early-phase clinical trials.To compare the safety and efficacy of prasugrel with those of clopidogrel in patients with acute coronary syndromes (ACS).TRITON-TIMI 38 was a randomized, phase III trial, conducted across 30 countries from November 2004 to January 2007. All patients were scheduled to undergo percutaneous coronary intervention (PCI) for ACS. For patients with unstable angina or non-ST-segment elevation myocardial infarction, the inclusion criteria were a Thrombolysis In Myocardial Infarction (TIMI) risk score of 3 or more, ischemic symptoms of 10 min duration or longer occurring within the 72 h before randomization, and either ST-segment deviation of 1 mm or more or elevated cardiac biomarkers. Patients with ST-segment elevation myocardial infarction (STEMI) were enrolled within 12 h of symptom onset if they were scheduled to undergo PCI within 14 days of the index event. The coronary anatomy of all patients was known. Exclusion criteria included anemia, thrombocytopenia, and treatment with a thienopyridine within the 5 days before enrollment. Patients were randomly assigned to receive a loading dose of either 60 mg prasugrel or 300 mg clopidogrel at any time from randomization to 1 h after catheterization, followed by maintenance doses of 10 mg/day prasugrel or 75 mg/day clopidogrel, in combination with 75-162 mg/day aspirin, for 6-15 months after PCI.The primary composite end point was cardiovascular death, nonfatal myocardial infarction (MI), or nonfatal stroke. The key primary safety end points were TIMI major or minor bleeding.A total of 13,608 patients were enrolled, 10,074 of whom had unstable angina or non-STEMI. The remaining 3,534 patients had STEMI. There were 6,813 patients in the prasugrel group and 6,795 in the clopidogrel group. Prior hypertension (64%) and hypercholesterolemia (56%) were prevalent in both groups. PCI was performed in 99% of patients, with the remainder undergoing CABG surgery. Over the course of the study period (15 months), more patients in the clopidogrel group experienced the primary efficacy end point than did patients in the prasugrel group (12.1% vs 9.9%, hazard ratio [HR] 0.81, 95% CI 0.73-0.90; P<0.001). In addition, the rates of stent thrombosis and MI were significantly lower in the prasugrel group than in the clopidogrel group (HRs 0.48 and 0.76, respectively; P<0.001 for both). Prasugrel was, however, associated with an increased risk of major or minor TIMI bleeding (HR 1.31; P = 0.002), including fatal (HR 4.19; P = 0.002) and life-threatening (HR 1.52; P = 0.01) bleeding. Prasugrel conferred a net clinical benefit when the cohort was considered as a whole, but in patients with prior stroke or transient ischemic attack prasugrel conferred a net harm, and elderly patients (≥75 years) and those weighing less than 60 kg had no net benefit.Prasugrel is associated with significant reductions in ischemic events when compared with clopidogrel in patients with ACS undergoing PCI, but also with an increased bleeding risk.