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Greater Inhibition of Platelet Aggregation and Reduced Response Variability With Prasugrel Versus Clopidogrel: An Integrated Analysis

Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana, weerakkody_govinda{at}lilly.com

Joseph A. Jakubowski, PhD

Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana

John T. Brandt, MD

Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana

Christopher D. Payne, MSc

Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana

Hideo Naganuma, PhD

Daiichi Sankyo Co, Ltd, Tokyo, Japan

Kenneth J. Winters, MD

Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana

Multiple studies report response variability to a 300-mg clopidogrel loading dose (LD). Pooled platelet aggregometry data compared responses (change in maximal platelet aggregation [MPA] or inhibition of platelet aggregation [IPA]) to clopidogrel 300-mg (n = 131) or prasugrel 60-mg (n = 109) LDs. Poor responder rates were determined using empiric criteria (IPA < 10% and MPA < 10% for 20 µM and 5 µM adenosine diphosphate [ADP]) and Bayesian model-based criteria (IPA < 20% and MPA < 15% for 20 µM ADP; IPA < 25% and MPA < 20% for 5 µM ADP). Prasugrel achieved greater MPA and IPA from 2 to 24 hours post-LD (P < .001). For 20 µM ADP, poor responder rates for clopidogrel ranged from 17% to 43%; no prasugrel poor responders were observed. Regardless of the criterion, prasugrel 60 mg achieved greater IPA and fewer poor responders than the clopidogrel 300-mg LD.

Key Words: clopidogrel • prasugrel • platelet aggregation • thienopyridines • resistance • P2Y12 • ADP

Journal of Cardiovascular Pharmacology and Therapeutics, Vol. 12, No. 3, 205-212 (2007)
DOI: 10.1177/1074248407304731


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