• What evidence suggests that proton pump inhibitors (PPIs) may reduce the cardiovascular benefits of clopidogrel (Plavix)?
• Why does new randomized controlled trial evidence not completely pertain to patients who take clopidogrel plus regular omeprazole?
• What PPI seems less likely to interact with clopidogrel?
• Does separating the timing of administration of clopidogrel and PPIs prevent the interaction?

Clopidogrel (Plavix) is a prodrug. It’s metabolized in the liver to the active form that inhibits platelet aggregation. Cytochrome P450 2C19 (CYP2C19) appears to be one of the enzymes involved in the activation of clopidogrel. Some proton pump inhibitors (PPIs) inhibit CYP2C19 metabolism. Patients who have a myocardial infarction (MI) or undergo stent placement and take clopidogrel are sometimes prescribed a prophylactic PPI to reduce the risk for GI bleeding. Retrospective studies first built a case that PPIs might reduce clopidogrel’s antiplatelet effect and increase the risk for cardiovascular events. However, the data from randomized controlled clinical trials suggest that adding a PPI to clopidogrel does not increase the risk for cardiovascular events. This document reviews the data for an interaction between PPIs and clopidogrel.