Lack of Significant Interactions Between Clopidogrel and Proton Pump Inhibitor Therapy: Meta-Analysis of Existing Literature

Published data regarding the effect of concomitant clopidogrel and proton pump inhibitor (PPI) therapy on cardiovascular outcomes have been conflicting. To perform an updated meta-analysis in order to determine changes in risk differences (RD) between primary and secondary outcome analyses. Primary analysis was based on definite vascular outcomes, including all cause mortality, cardiac death, myocardial infarction, and/or stroke. Secondary analysis also incorporated probable cardiac events, which included re-hospitalization for cardiac symptoms or revascularization procedures. RD were combined using a random-effects model. We reviewed 1,204 publications of which 26 studies (16 published articles, 10 abstracts) met inclusion criteria. The meta-analysis of outcomes from the two randomized controlled trials did not show an increased risk (RD 0.0, 95% CI -0.01, 0.01) for adverse outcomes. The meta-analysis of primary outcomes showed a RD of 0.02 (95% CI 0.01, 0.03) for all studies. The meta-analysis for secondary outcomes yielded a RD of 0.02 (95% CI 0.01-0.04) based on 19 published papers and abstracts. When primary and secondary outcomes were combined, the meta-analysis for published papers yielded an overall RD of 0.05 (95% CI 0.03-0.06). In patients using concomitant clopidogrel and PPI therapy, the risk of adverse cardiac outcomes was 0% based on data from well-controlled randomized trials. Data from retrospective studies and the addition of probable vascular events significantly increased the RD estimates, likely due to lack of adjustment for potential confounders.