December 8, 2009—Jeremy A. Rassen, ScD, et al, noted that recent studies have raised concerns about the reduced efficacy of clopidogrel when used concurrently with proton pump inhibitors (PPIs); however, those studies may have overestimated the risk. Therefore, the investigators studied the potential for increased risk of adverse cardiovascular events among users of clopidogrel with or without concurrent use of PPIs in three large cohorts of patients 65 years of age, who were treated between 2001 and 2005. The study was published in Circulation (2009;120:2322-2329).

According to the investigators, 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. The investigators recorded myocardial infarction hospitalization, death, and revascularization among PPI users and nonusers. They then assessed the primary endpoint of myocardial infarction hospitalization or death using cohort-specific and pooled regression analyses. The analysis was composed of 18,565 clopidogrel users. On a pooled basis, 2.6% of those who 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 endpoint of myocardial infarction or death was 1.22 (95% confidence interval [CI], 0.99–1.51), for death was 1.20 (95% CI, 0.84–1.70), and for revascularization was 0.97 (95% CI, 0.79–1.21). Matched analyses generally yielded similar results.

Although point estimates indicated a slightly increased risk of myocardial infarction hospitalization or death in older patients initiating both clopidogrel and a PPI, the investigators did not observe conclusive evidence of a clopidogrel–PPI interaction of major clinical relevance. The data suggest that if this effect exists, it is unlikely to exceed a 20% risk increase, the investigators concluded.