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 12 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.