Background: Recent studies have raised concerns about the reduced efficacy of clopidogrel when used concurrently with proton pump inhibitors (PPIs), but those studies may have overestimated the risk.
Methods and results: We studied the potential for increased risk of adverse cardiovascular events among users of clopidogrel with versus without concurrent use of PPIs in 3 large cohorts of patients > or =65 years of age, treated between 2001 and 2005. All patients had undergone percutaneous coronary intervention or had been hospitalized for acute coronary syndrome in Pennsylvania, New Jersey, or British Columbia, and subsequently had initiated treatment with clopidogrel. We recorded myocardial infarction hospitalization, death, and revascularization among PPI users and nonusers. We assessed our primary end point of myocardial infarction hospitalization or death using cohort-specific and pooled regression analyses. We entered 18 565 clopidogrel users into our analysis. On a pooled basis, 2.6% of those who also initiated a PPI versus 2.1% of PPI nonusers had a myocardial infarction hospitalization; 1.5% versus 0.9% died; and 3.4% versus 3.1% underwent revascularization. The propensity score-adjusted rate ratio for the primary end point of myocardial infarction or death was 1.22 (95% confidence interval, 0.99 to 1.51); for death, 1.20 (95% confidence interval, 0.84 to 1.70); and for revascularization, 0.97 (95% confidence interval, 0.79 to 1.21). Matched analyses generally yielded similar results.
Conclusions: Although point estimates indicated a slightly increased risk of myocardial infarction hospitalization or death in older patients initiating both clopidogrel and a PPI, we did not observe conclusive evidence of a clopidogrel-PPI interaction of major clinical relevance. Our data suggest that if this effect exists, it is unlikely to exceed a 20% risk increase.