Korean J Med.  2011 Jul;81(1):26-33.

Drug Interaction between Proton Pump Inhibitors and Clopidogrel: Safe Perspective

• Jo YJ

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.

Keyword

Proton pump inhibitor; Clopidogrel; Drug interactions

MeSH Terms

Acute Coronary Syndrome
Biomarkers
Blood Platelets
Cytochrome P-450 Enzyme System
Drug Interactions
Hemorrhage
Omeprazole
Platelet Aggregation
Proton Pump Inhibitors
Proton Pumps
Protons
Risk Assessment
Ticlopidine
Cytochrome P-450 Enzyme System
Omeprazole
Proton Pump Inhibitors
Proton Pumps
Protons
Ticlopidine