The Onset of Inhibition of Platelet Aggregation With Prasugrel Compared With Clopidogrel Loading Doses Using Gatekeeping Analysis of Integrated Clinical Pharmacology Data

The purpose of this analysis was to determine the time by which a prasugrel 60-mg loading dose (LD) achieved significantly greater inhibition of platelet aggregation (IPA) than the peak IPA after a clopidogrel 300-mg LD or 600-mg LD. Data were pooled from nine studies representing 587 individuals: 274 healthy subjects and 313 patients with stable coronary artery disease. The primary pharmacodynamic measure was IPA using 20 mu M adenosine-5`-diphosphate as the agonist. Gatekeeping analysis compared the peak IPA at 4, 6, and 24 hours after a clopidogrel 300-mg or 600-mg LD with IPA at various prior time points backwards after a prasugrel LD until a statistically nonsignificant difference was reached. Prasugrel 60-mg LD produced greater IPA by 30 minutes than the peak IPA after a clopidogrel 300-mg LD (P < 0.0001). Significantly greater IPA was achieved at 1 hour after prasugrel 60-mg LD compared with the peak IPA after 600-mg clopidogrel LD (P < 0.0001), regardless of sex, body weight, or age and as early as 30 minutes in the diabetic subgroup. A prasugrel 60-mg LD produces significantly faster onset and greater IPA compared with a clopidogrel 300-mg LD or 600-mg LD.