Among patients with acute coronary syndromes (ACS) without ST-segment elevation who were treated without revascularization, prasugrel was associated with lower platelet reactivity than clopidogrel, irrespective of age, weight, and dose.  However, no significant difference was seen between platelet reactivity and occurrence of ischemic outcomes according to a study presented during a Late Breaking Clinical Trials session at the American Heart Association's Scientific Sessions 2012 and simultaneously published Online First in JAMA.

Paul A. Gurbel, M.D., of the Sinai Center for Thrombosis Research, Baltimore, and colleagues conducted a study to examine the differences in platelet reactivity and clinical outcomes among patients with acute coronary syndromes (ACS) being treated by the antiplatelet agents clopidogrel or prasugrel.

The investigators conducted a large serial platelet function substudy within the Targeted Platelet Inhibition to Clarify the Optimal Strategy to Medically Manage Acute Coronary Syndromes (TRILOGY ACS) trial.  It was a randomized, double-blind, active control, event-driven trial comparing prasugrel vs. clopidogrel therapy in patient with unstable angina or non-ST-segment elevation myocardial infarction who were management medically without planned revascularization.

The objectives of the study were to characterize differences in platelet reactivity between treatment groups over time, to delineate the relationship of platelet reactivity with ischemic end point occurrence, and to determine a threshold for high platelet reactivity that optimizes the ability to discriminate between patients with and without ischemic event occurrence.

From 2008 to 2011, patients with medically managed unstable angina or non-ST-segment elevation myocardial infarction (NSTEMI) were enrolled in the TRILOGY ACS trial comparing clopidogrel vs. prasugrel. Of 9,326 participants, 27.5 percent were included in a platelet function substudy, including 1,286 who received prasugrel and 1,278 who received clopidogrel. Patients were randomized to receive aspirin with either prasugrel (10 or 5 mg/d) or clopidogrel (75 mg/d); those 75 years or older or younger than 75 years but who weighed less than 132 lbs. received a 5-mg prasugrel maintenance dose.

The researchers found that "among patients with ACS without ST-segment elevation and initially managed without revascularization, prasugrel was associated with lower platelet reactivity than clopidogrel, irrespective of age, weight, and dose. Among those in the platelet substudy, no significant differences existed between prasugrel vs. clopidogrel in the occurrence of the primary efficacy end point [composite of cardiovascular death, heart attack, or stroke] through 30 months and no significant association existed between platelet reactivity and occurrence of ischemic outcomes."

The TRILOGY ACS study was funded by Eli Lilly and Daiichi Sankyo.  Author disclosures are in the manuscript.