Pharmacodynamic assessment of a novel P2Y12 receptor antagonist in Japanese patients with coronary artery disease undergoing elective percutaneous coronary intervention.

Introduction: Numerous reports have shown that prasugrel shows a rapid and consistent antiplatelet effect among European and US patients. Previous studies suggest that prasugrel might be expected to achieve an adequate antiplatelet effect in healthy Asian subjects, even at lower doses than those assessed in the TRITON-TIMI 38 study. In this study, the antiplatelet effect of prasugrel was evaluated in Japanese coronary artery disease (CAD) patients undergoing percutaneous coronary intervention (PCI).

Methods And Results: Eighty-four patients were randomized into four treatment groups: prasugrel 10/2.5mg (loading dose [LD]/maintenance dose [MD]), 15/3.75 mg or 20/5mg, and clopidogrel 300/75 mg. The LD of each regimen was administered the day before PCI, followed by 28-day MD on aspirin background therapy (81-100mg). Antiplatelet effects were evaluated by light transmission aggregometry and VASP assay. The mean inhibition of platelet aggregation (IPA) induced by 20 μM of adenosine diphosphate at 4 hours after LD was higher among the prasugrel 10/2.5mg, 15/3.75 mg and 20/5mg groups compared with the clopidogrel group (12.3%, 20.9%, 29.8% vs. 8.4%, respectively). The proportion of subjects with an IPA of <10% on Day 28 was lower among the prasugrel 15/3.75 mg, and 20/5mg groups than in the clopidogrel group (0%, 6.3% vs. 15.8%, respectively). No "major" or "clinically relevant non-major" bleeding was observed.

Conclusions: Prasugrel 15 mg LD/3.75 mg MD or higher doses was well tolerated and achieved a more rapid, higher and consistent antiplatelet effect than clopidogrel in Japanese CAD patients undergoing PCI.