Authors
Bhatt DL, Cryer BL, Contant CF, et al.
Title
Clopidogrel with or without omeprazole in coronary artery disease.
References
N Engl J Med 2010;363:1909-17.
Background
Gastrointestinal complications are an important problem of antithrombotic therapy. Proton-pump inhibitors (PPIs) are believed to decrease the risk of such complications, though no randomized trial has proved this in patients receiving dual antiplatelet therapy. Recently, concerns have been raised about the potential for PPIs to blunt the efficacy of clopidogrel.
Purpose
To assess the efficacy and safety of concomitant administration of clopidogrel and PPIs in patients with coronary artery disease who are receiving clopidogrel plus aspirin.
Design
  • Randomized Safety/Efficacy Study, Double Blind
  • Patients included if use of Clopidogrel and ASA expected for at least 12 months, including patients with acute coronary syndromes and patients undergoing PCI
  • Primary gastrointestinal end point: composite of overt or occult bleeding, symptomatic gastroduodenal ulcers or erosions, obstruction, or perforation.
  • The primary cardiovascular end point was a composite of death from cardiovascular causes, nonfatal myocardial infarction, revascularization, or stroke.
Exclusion Criteria
  • Anticipated hospitalization >48h
  • Clinical need for short-term or long-term use of a PPI
Follow-Up
180 days. The study terminated prematurely when the sponsor lost funding.
Treatment Regimen
Patients were randomly assigned with an indication for dual antiplatelet therapy to receive clopidogrel in combination with either omeprazole or placebo, in addition to aspirin.
Results
Primary Endpoints:
  • Planned to enroll 5000 patients; 3873 were randomized and 3761 were included in analyses
  • Less gastrointestinal events with omeprzole. Hazard ratio with omeprazole, HR 0.34, 95%CI 0.18 to 0.63; P<0.001)
  • No difference in cardiovascular events HR 0.99; 95% CI, 0.68 to 1.44; P=0.96

Secondary Endpoints:

  • No difference in serious adverse events
Summary
Among patients receiving aspirin and clopidogrel, prophylactic use of a PPI reduced the rate of upper gastrointestinal bleeding.
There was no apparent cardiovascular interaction between clopidogrel and omeprazole, but the results do not rule out a clinically meaningful difference in cardiovascular events due to use of a PPI.
Implications
Unclear. The study was aborted prematurely. PPI use may reduce upper GI bleeding. Interaction with clopidogrel remains unclear from this study. It is also unclear from this study if the potential interaction(s) would have effects on the cardiovascular event rates.
Related Figures
None.