CYP2C19 Genotype and Proton Pump Inhibitors in Clopidogrel-Treated Patients

debate continues regarding the existence of an adverse interaction between proton pump inhibitors (PPIs) and clopidogrel. Concerns for a drug-drug interaction first emerged when experimental pharmacodynamic data indicated that omeprazole might diminish the in vitro antiplatelet effects of clopidogrel. 1,2 These concerns were escalated when retrospective data from 2 large observational studies demonstrated that use of a PPI was associated with an increased risk of cardiovascular events for patients treated with clopidogrel. In response to these findings, the US Food and Drug Administration updated the drug's label to warn that the effectiveness of clopidogrel is reduced when administered in combination with omeprazole. 5 However, these findings have since been disputed by a growing number of analyses from clinical trial populations that have failed to show an increased risk of adverse outcomes when PPIs are administered in combination with clopidogrel. 6 -8 Furthermore, the results of the only randomized clinical trial to address this issue demonstrated similar cardiovascular risk regardless of whether subjects were assigned to clopidogrel alone or in combination with omeprazole. 9