Effects of PPIs and an H2 blocker on the Antiplatelet Function of Clopidogrel in Japanese Patients under Dual Antiplatelet Therapy

摘要

Aim: Dual antiplatelet therapy (DAPT) with aspirin and clopidogrel is essential after percutaneous coronary intervention (PCI). Clopidogrel is a prodrug and changed into active metabolite by cytochrome p450 enzymes (CYPs), especially CYP2C19. Proton pump inhibitors (PPIs) are used for the prevention of aspirin-induced gastrointestinal bleeding. PPIs are also metabolized by CYP2C19, although the degree of its contribution is dependent on the kind of PPI. Omeprazole, a PPI, has been reported to weaken the antiplatelet effects of clopidogrel. Famotidine, a histamine receptor type 2 (H2) blocker, could also be an alternative to PPIs. The aim of this study was to evaluate the effects of PPIs and an H2 blocker on the antiplatelet function of clopidogrel. Methods: Patients receiving DAPT due to prior PCI, who took either omeprazole or rabeprazole, were enrolled ( n =25). The initial PPI was changed to the other PPI as a crossover study. In another study, patients undergoing DAPT without taking PPIs or H2 blockers were enrolled ( n =30) and famotidine was added. Results: Platelet aggregability when taking omeprazole was higher than when taking rabeprazole, evaluated by an optical aggregometer using collagen as a stimulus ( p =0.0051) and by the VerifyNow P2Y12 assay ( p =0.0060). Platelet aggregability when taking rabeprazole was comparable to that in control patients ( n =15). Concomitant use of famotidine had no effect. Conclusion: Omeprazole significantly reduced the antiplatelet effect of clopidogrel and this effect on clopidogrel was stronger than that of rabeprazole. Concomitant use of famotidine had no effect on the antiplatelet effect of clopidogrel.