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Observational and platelet reactivity studies suggest that proton-pump inhibitors (PPIs) inhibit clopidogrel's antiplatelet effects (JW Cardiol Sep 1 2009). Should patients taking clopidogrel avoid PPIs; switch to another antiplatelet agent; or, in the absence of definitive trial findings, continue using the drugs together despite warnings from many directions? To address the lack of trial evidence, the COGENT investigators randomized 3873 patients (mean age, 68; 68% men) requiring dual antiplatelet therapy to receive clopidogrel plus either omeprazole or placebo (both groups received aspirin). The primary cardiovascular endpoint was a composite of cardiovascular death, nonfatal myocardial infarction, coronary revascularization, and stroke.
The rate of gastrointestinal (GI) events at 180 days was lower in the omeprazole group than in the placebo group (1.1% vs. 2.9%; hazard ratio, 0.34; 95% confidence interval, 0.18–0.63; P<0.001). The rate of the primary cardiovascular endpoint was similar in the two groups (4.9% and 5.7%; HR, 0.99; 95% CI, 0.68–1.44; P=0.96). Adverse event rates were also similar between the two groups.
Bhatt DL et al. for the COGENT Investigators. Clopidogrel with or without omeprazole in coronary artery disease. N Engl J Med 2010 Oct 6; [e-pub ahead of print]. (http://www.nejm.org/doi/full/10.1056/NEJMoa1007964)
Comment
COGENT failed to show that patients treated with omeprazole, clopidogrel, and aspirin had more cardiovascular events than those treated with clopidogrel and aspirin alone. Opinions about the use of PPIs and clopidogrel are likely to continue to diverge: Some readers will conclude that the previous platelet reactivity findings do not translate into variances in clinical outcomes; others will discount the current study as lacking power to detect clinically meaningful differences. With regard to reducing GI bleeding rates, these results support a small absolute benefit for PPI use in patients on dual antiplatelet therapy.