Antiplatelet therapy and proton pump inhibition: cause for concern?

To review the current evidence on the clinical significance of the drug-drug interactions between the available antiplatelet agents and proton pump inhibitors (PPIs).

Gastrointestinal bleeding is associated with higher rates of morbidity and mortality following a myocardial infarction. PPIs are commonly used to prevent gastrointestinal bleeding. PPIs can attenuate metabolism of clopidogrel to its active metabolite by inhibiting various hepatic CYP450 enzymes, mainly CYP2C19. Concomitant use of a PPI with clopidogrel reduces clopidogrel active metabolite generation and subsequent platelet inhibition. In observational studies, the clinical significance of this drug-drug interaction is mixed. Evidence from the only randomized trial studying the clinical implications of the PPI-clopidogrel interaction did not demonstrate any difference in cardiovascular outcomes but did show a reduction in gastrointestinal bleeding with use of a PPI.

The drug-drug interaction between antiplatelet agents and PPIs at the enzymatic level does not seem to result in worse clinical outcomes. The risk of gastrointestinal bleeding with antiplatelet therapy is substantial. Clinicians should use PPIs in selected high-risk patients to prevent gastrointestinal bleeding.