Impact of proton pump inhibitors on the effectiveness of clopidogrel after coronary stent placement: the clopidogrel Medco outcomes study

Pharmacotherapy. 2010 Aug;30(8):787-96. doi: 10.1592/phco.30.8.787.


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.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Aged
  • Angioplasty, Balloon, Coronary* / adverse effects
  • Cardiovascular Diseases / drug therapy*
  • Cardiovascular Diseases / etiology
  • Cardiovascular Diseases / surgery*
  • Clopidogrel
  • Cohort Studies
  • Drug Synergism
  • Drug Therapy, Combination
  • Female
  • Hospitalization / trends
  • Humans
  • Male
  • Middle Aged
  • Proton Pump Inhibitors / administration & dosage*
  • Proton Pump Inhibitors / adverse effects
  • Retrospective Studies
  • Stents*
  • Ticlopidine / administration & dosage
  • Ticlopidine / adverse effects
  • Ticlopidine / analogs & derivatives*
  • Treatment Outcome


  • Proton Pump Inhibitors
  • Clopidogrel
  • Ticlopidine