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ESTHER J. LAST, PHARM.D., is Clinical Pharmacist, Clarian Health, Indianapolis, IN; at the time of writing she was Drug Information Resident and Adjunct Assistant Professor of Pharmacy Practice, School of Pharmacy and Pharmaceutical Science, Purdue University, West Lafayette, IN. AMY HECK SHEEHAN, PHARM.D., is Drug Information Specialist, Clarian Health, and Associate Professor of Pharmacy Practice, School of Pharmacy and Pharmaceutical Science, Purdue University.

Address correspondence to Dr. Last at Clarian Health, Department of Pharmacy, 1701 N. Senate Boulevard, Room AG401, Indianapolis, IN 46202 (elast{at}clarian.org).

Purpose. Recent evidence of a potential interaction between clopidogrel and proton pump inhibitors (PPIs) is discussed. Summary. The American College of Cardiology and the American Heart Association recommend use of gastroprotective agents, specifically PPIs, in patients receiving aspirin, a thienopyridine, or the combination who have an increased risk for recurrent gastrointestinal bleeding. Available evidence from one small, short-term, randomized, double-blind trial evaluating platelet aggregation and several observational studies suggests that there is a potential for a clinically significant interaction between clopidogrel and PPIs. A post hoc analysis of a large, randomized, double-blind trial found no evidence of a clinically significant drug interaction at 28 days, though a significant difference was observed at one year. The authors concluded that the use of PPIs, regardless of clopidogrel use, increases the risk of adverse cardiovascular events. Conclusion. Although data are limited, observational studies and prospective trials involving surrogate markers of platelet reactivity suggest a clinically significant interaction between clopidogrel and PPIs. Until further studies are completed to delineate the specifics of the interaction between clopidogrel and PPIs, the risks and benefits of concomitant treatment should be carefully weighed to determine the most appropriate treatment for each individual patient. Index terms: Cardiovascular diseases; Clopidogrel; Drug interactions; Gastrointestinal drugs; Platelet aggregation inhibitors; Toxicity