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ACC: Platelet Inhibition More Consistent With Prasugrel Than Clopidogrel By Jill Stein ORLANDO, FL -- March 14, 2005 -- Prasugrel (CS-747, LY640315) produces a greater and more consistent level of inhibition of platelet aggregation compared with clopidogrel. Data presented here March 9th at the American College of Cardiology 54th Scientific Session indicate that platelet aggregation response at 4 and 24 hours was greater with a 60-mg dose of prasugrel than with a 300-mg dose of clopidogrel. Prasugrel is an investigational oral thienopyridine antiplatelet agent that blocks the P2Y12 adenosine diphosphate receptor that inhibits platelet activation and aggregation mediated by this receptor. In preclinical studies, loading doses of prasugrel achieved greater levels of adenosine diphosphate-induced inhibition of platelet activation more rapidly than did clopidogrel. In addition, prasugrel was found to have 10-fold greater potency than clopidogrel, said the study's lead investigator John T. Brandt, MD, a senior level physician at Eli Lilly and Company, Indianapolis, Indiana. "There is notable variation in pharmacodynamic response to clopidogrel, as measured by platelet aggregation or other platelet function tests," Dr. Brandt said. "Patients with a low level of platelet inhibition in response to clopidogrel may be at increased risk of major adverse cardiac events." In the study, 68 healthy subjects were randomized to receive either a 60-mg loading dose of prasugrel or a 300-mg loading dose of clopidogrel in a two-way crossover design. The researchers measured maximal platelet aggregation and inhibition of platelet aggregation. Responder rates were determined by two methods: 1) >25% inhibition of platelet aggregation at four and 24 hours, and 2) >10% decrease in maximal platelet aggregation at 4 and 24 hours. By either definition, prasugrel achieved superior responder rates compared with clopidogrel. All patients treated with prasugrel had more than 25% inhibition of platelet aggregation at 4 hours compared with 42.4% of patients treated with clopidogrel (P <.001). All the prasugrel recipients and 68.2% of clopidogrel recipients had more than 10% maximal platelet aggregation at 4 hours (P <.001). Inhibition of platelet aggregation at 4 hours was 78.4% with prasugrel and 31.7% with clopidogrel (P <.001). Among the clopidogrel responders, defined as those subjects with more than 25% inhibition of platelet aggregation at 4 and 24 hours, inhibition of platelet aggregation at 4 hours was superior with prasugrel compared with clopidogrel (79.2% versus 52.5%; P <.001). Among clopidogrel nonresponders, inhibition of platelet aggregation at 4 hours was 78.0% with prasugrel and 17.6% with clopidogrel (P <.001). Similar differences between the two agents in inhibition of platelet aggregation were observed at 24 hours, said Dr. Brandt. The study was sponsored by Eli Lilly Company and Sankyo. [Presentation title: Superior Responder Rate for Inhibition of Platelet Aggregation With a 60 mg Loading Dose of Prasugrel (CS-747, LY640315) Compared With a 300 mg Loading Dose of Clopidogrel. Abstract 868-5] E-mail this page to a friend or colleague! To print, use this version