Evidence for interaction between clopidogrel and proton-pump inhibitors

Abstract

Last and Sheehan1 provided an excellent review of the laboratory and clinical evidence surrounding the interaction between clopidogrel and proton-pump inhibitors (PPIs),1 but we disagree with their conclusion that the risks and benefits of concomitant clopidogrel and PPI use should be carefully evaluated on an individual basis. The most robust studies to date demonstrate that there is no clinically significant drug interaction between clopidogrel and PPIs. The Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition with Prasugrel—Thrombolysis in Myocardial Infarction (TRITON–TIMI) 38 recently analyzed by O’Donoghue et al.,2 was a large, randomized controlled study, and its results clearly demonstrated no clinically meaningful drug interaction between clopidogrel and PPIs. In addition, data from the landmark COGENT study, which compared clopidogrel and omeprazole with clopidogrel alone in a randomized, double-blind fashion, were recently presented.3 That trial also demonstrated no increase in cardiac event rates in patients receiving clopidogrel and omeprazole compared with those receiving clopidogrel alone and further indicates that there is no clinically significant drug interaction. The current prevailing opinion among leading cardiologists and the latest American College of Cardiology update on ST-elevation myocardial infarction holds that it has been definitively demonstrated that there is no clinically significant drug interaction between clopidogrel and PPIs.4,5