Randomized, Double-Blind, Dose-Finding, Phase II Study of Prasugrel in Japanese Patients Undergoing Elective Percutaneous Coronary Intervention.

AIM Prasugrel is a novel platelet P2Y12 receptor blocker with a faster onset of action and greater platelet inhibition with less response variability than clopidogrel. Our objective was to determine the optimal prasugrel dose in Japanese patients undergoing elective percutaneous coronary intervention (PCI) with respect to the incidence of bleeding and platelet inhibition. METHODS A total of 422 patients were randomly assigned to receive clopidogrel or prasugrel in two strata (standard group: ＜75 years of age and body weight ＞50 kg, n=312; high-risk group: ≥75 years of age and/or body weight ≤50 kg, n=110). The standard group received 20/3.75 or 20/5mg (loading/maintenance doses for three months) of prasugrel or 300/75mg of clopidogrel, while the high-risk group received 20/2.5 or 20/3.75mg of prasugrel or 300/75mg of clopidogrel. RESULTS The rates of TIMI major and minor bleeding (primary endpoint) were similar among the three treatment arms in the standard group (20/5mg of prasugrel: 0%; 20/3.75mg of prasugrel: 3.8%; 300/75mg of clopidogrel: 2.9%) and the high-risk group (20/3.75mg of prasugrel: 2.7%; 20/2.5mg of prasugrel: 0%; 300/75mg of clopidogrel: 2.8%). VerifyNow assays revealed sufficient levels of platelet inhibition at Weeks 4 and 12 in both the prasugrel arms of the standard group and the 20/3.75mg of prasugrel arm in the high-risk group. Platelet inhibition was not affected by the CYP2C19 phenotype in the prasugrel groups. CONCLUSIONS The prasugrel dosing regimen of 20/3.75mg has strong antiplatelet effects and the risk of bleeding events is low in Japanese patients undergoing PCI.