Impact of Proton Pump Inhibitors on the Effectiveness of Clopidogrel After Coronary Stent Placement: The Clopidogrel Medco Outcomes Study

Study Objective. To investigate the potential impact of proton pump inhibitors (PPIs) on the effectiveness of clopidogrel in preventing recurrent ischemic events after percutaneous coronary intervention (PCI) with stent placement. Design. Population-based, retrospective cohort study. Data Source. National medical and pharmacy benefit claims database comprising approximately 19 million members. Patients. A total of 16,690 patients who had undergone PCI with stent placement and who were highly adherent to clopidogrel therapy alone (9862 patients) or to clopidogrel with a PPI (6828 patients) between October 1, 2005, and September 30, 2006. Measurements and Main Results. The primary end point was the occurrence of a major adverse cardiovascular event during the 1.2 months after stent placement. These events were defined as hospitalization for a cerebrovascular event (stroke or transient ischemic attack), an acute coronary syndrome (myocardial infarction or unstable angina), coronary revascularization (PCI or coronary artery bypass graft), or cardiovascular death. A composite event rate was compared between patients who received clopidogrel alone and those who received concomitant clopidogrel-PPI therapy. Baseline differences in covariates were adjusted by using Cox proportional hazards models. In the 9862 patients receiving clopidogrel alone, 1766 (17.9%) experienced a major adverse cardiovascular event compared with 1710 patients (25.0%) who received concomitant clopidogrel-PPI therapy (adjusted hazard ratio 1.51, 95% confidence interval 1.39-1.64, p<0.0001). Similar associations of increased risk were observed for each PPI studied (omeprazole, esomeprazole, pantoprazole, and lansoprazole). Conclusion. Concomitant use of a PPI and clopidogrel compared with clopidogrel alone was associated with a higher rate of major adverse cardiovascular events within 1 year after coronary stent placement.