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Drug Interaction between Proton Pump Inhibitors and Clopidogrel: Safe Perspective  

Jo, Yun-Ju (Department of Internal Medicine, Eulji University School of Medicine)
Publication Information
The Korean Journal of Medicine / v.81, no.1, 2011 , pp. 26-33 More about this Journal
Abstract
Clopidogrel prevent atherothrombotic complications following acute coronary syndromes by inhibiting platelet aggregation. However, in case of concomitant use of clopidogrel and proton pump inhibitor (PPI) for prophylaxis of gastrointestinal (GI) bleeding, the anti-clotting of clopidogrel will be decreased because PPI inhibit competitively cytochrome P450 enzymes, especially CYP2C19. Through several pharmacodynomic studies, omeprazole, but not other PPIs, worsens surrogate markers (e.g., platelet reactivity index) of clopidogrel efficacy. And many observational studies show concomitant use of clopidogrel and PPI have increased the risks of cardiovascular (CV) events (hazard/odds ratios = 1.25-1.5). However, only one prospective randomized trial (COGENT trial) of omeprazole vs. placebo in clopidogrel users show no difference in CV events (hazard ratio = 1.02) and decrease the risk of GI bleeding (hazard ratio = 0.13). Further well designed research will need to determine whether a pharmacodynamic effect of clopidogrel affected by PPI will be changed clinical CV events. Clinical decisions about concomitant use of PPI and clopidogrel must be balance overall risks and benefits, considering both CV and GI complications.
Keywords
Proton pump inhibitor; Clopidogrel; Drug interactions;
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