ACC: Prasugrel Shows Better Platelet Inhibition Than Clopidogrel
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ACC: Prasugrel Shows Better Platelet Inhibition Than Clopidogrel

By Jill Stein

ORLANDO, FL -- March 9, 2005 -- Aspirin-treated subjects with atherosclerotic disease can achieve better protection from platelet aggregation with prasugrel with comparable safety compared to the standard regimen of clopidogrel.

In a clinical study presented here March 8th at the American College of Cardiology 54th Scientific Session, researchers demonstrated that prasugrel (CS-747, LY640315), at a 40 to 60 mg loading dose and 7.5 to 10 mg maintenance dose, is more effective and as safe as clopidogrel at a 300 mg loading dose and 75 mg maintenance dose regimen.

Prasugrel is an investigational oral antiplatelet agent designed to prevent platelet activation by blocking adenosine diphosphate receptors on the platelet surface. Clopidogrel, a thienopyridine derivative, is standard therapy after coronary stenting.

In their study, Lars Wallentin, MD, professor of cardiology, Uppsala Clinical Research Center, Uppsala, Sweden, and colleagues randomized 101 subjects to one of five oral dosing regimens (four prasugrel dosing regimens and one clopidogrel dosing regimen).

All subjects participated in a 7-day run-in period on 325 mg aspirin prior to randomization. They had stable atherosclerosis and one of the following: coronary artery disease, a history of peripheral artery occlusive disease, and a history of cerebrovascular disease.

Results show that patients receiving 40 and 60 mg loading doses of prasugrel achieved significantly higher levels of platelet inhibition compared to those on 300 mg loading dose of clopidogrel (P <.05).

After 28 days, patients on 10 mg or 15 mg maintenance dose of prasugrel achieved higher levels of platelet inhibition than did those on the 75 mg clopidogrel maintenance dose of (P </=.0002).

There was a trend towards more bruising and minor bleeding with the 15 mg maintenance dose of prasugrel.

Overall adverse events with prasugrel 40 mg to 60 mg loading dose and 7.5 to 10 mg maintenance dose in this study were comparable to those seen with standard clopidogrel therapy.

Dr. Wallentin said that the study supports the selection of the 60 mg loading dose/10 mg maintenance dose of prasugrel for evaluation in the ongoing Thrombolysis in Myocardial Infarction (TIMI)-38 phase 3 clinical trial. TIMI-38 is comparing prasugrel and clopidogrel in up to 13,000 patients with acute coronary syndrome who are scheduled for percutaneous coronary intervention.

The study was sponsored by Eli Lilly and Company and Sankyo.

[Presentation title: Inhibition of Platelet Aggregation with Prasugrel (CS-747, LY640315), A Novel Thienopyridine P2Y12 Receptor Antagonist, Compared with Clopidogrel in Aspirin-Treated Patients with Atherosclerotic Vascular Disease. Abstract 1126-136]

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