Treatment with clopidogrel and proton pump inhibitors in combination: a review of emerging evidence

Abstract

Proton pump inhibitors often are prescribed in com-bination with clopidogrel to decrease risk of gastro-intestinal bleeding after acute coronary syndrome. Clopidogrel is a prodrug that has to be metabolized in the liver to generate the active metabolite. Both medications are metabolized largely by the CYP2C19 enzyme; therefore, concerns exist that a drug-drug interaction during concomitant treatment with clopi-dogrel and a proton pump inhibitor may result in reduction of platelet inhibition. We have reviewed ob-servational and randomized control studies that have evaluated the potential influence of proton pump in-hibitors on the platelet inhibitory effect of clopidogrel, along with cardiovascular outcomes. We also have sum-marized regulatory and academic guidelines for treat-ment of patients in which concomitant therapy with clopidogrel and proton pump inhibitors may be indi-cated. Confounding issues, including differential effects of individual proton pump inhibitors on the pharma-codynamics of clopidogrel and variation in clopido-grel metabolism mediated by CYP2C19 gene polymor-phisms, also are discussed.