Clopidogrel with or without omeprazole in coronary artery disease?

January 01, 0001

Clopidogrel with or without omeprazole in coronary artery disease?

These US and Spanish authors randomly assigned patients with an indication for dual antiplatelet therapy to receive clopidogrel in combination with either omeprazole or placebo, in addition to aspirin. The primary gastrointestinal end point was a 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. The trial was terminated prematurely when the sponsor lost financing.

They report: "We planned to enroll about 5000 patients; a total of 3873 were randomly assigned and 3761 were included in analyses. In all, 51 patients had a gastrointestinal event; the event rate was 1.1% with omeprazole and 2.9% with placebo at 180 days (hazard ratio with omeprazole, 0.34). The rate of overt upper gastrointestinal bleeding was also reduced with omeprazole as compared with placebo (hazard ratio, 0.13). A total of 109 patients had a cardiovascular event, with event rates of 4.9% with omeprazole and 5.7% with placebo (hazard ratio with omeprazole, 0.99, NS); high-risk subgroups did not show significant heterogeneity. The two groups did not differ significantly in the rate of serious adverse events, though the risk of diarrhea was increased with omeprazole."

The authors concluded: "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 our results do not rule out a clinically meaningful difference in cardiovascular events due to use of a PPI."

The question of reduced efficacy of antiplatelet therapy when PPI is used concurrently is not yet settled. These results suggest no.

For the full abstract, click here.

N Engl J Med 363:1909-1917, 11 November 2010
© 2010 to the Massachusetts Medical Society
Clopidogrel with or without Omeprazole in Coronary Artery Disease. Deepak L. Bhatt, Byron L. Cryer, Charles F. Contant, et al. Correspondence to Dr. Bhatt: [email protected]

Category: K. Circulatory, B. Blood/Blood Forming Organs/Immune Mechanisms, D. Digestive. Keywords: antiplatelet therapy, aspirin, clopidogrel, omeprazole, proton pump inhibitor, PPI, cardiovascular outcomes, randomized controlled trial, journal watch.
Synopsis edited by Dr Linda French, Toledo, Ohio. Posted on Global Family Doctor 30 November 2010

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