Interactions Between PPIs and Clopidogrel Are Clinically Unimportant

The prodrug clopidogrel is metabolized to its active form primarily by cytochrome P₄₅₀ 2C19. Proton-pump inhibitors (PPIs) inhibit this enzyme, and laboratory evidence suggests that concomitant use of clopidogrel and PPIs attenuates clopidogrel activity. The clinical effect of this interaction has been inconsistent in observational studies, but, in the one large randomized trial (JW Cardiol Oct 6 2010), PPI therapy did not raise risk for adverse cardiac outcomes in clopidogrel-treated patients.

A new observational study involved more than 24,000 patients who were prescribed clopidogrel and aspirin; 50% also were prescribed PPIs at some point during the study. After adjustment for multiple factors, PPI exposure was associated with 37% higher …