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Omeprazole Reduces Effectiveness of Clopidogrel on Platelet Function



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Am Fam Physician. 2008 Nov 15;78(10) Online.

Background: Clopidogrel (Plavix) is used in combination with aspirin in the prevention of atherothrombotic conditions, especially following placement of stents. Activation of clopidogrel requires several steps, mediated mainly by cytochrome P450 isoenzymes. Because one of these isoenzymes, CYP2C19, is also involved in the metabolism of proton pump inhibitors (PPIs), the use of PPIs such as omeprazole (Prilosec) could reduce the biologic effectiveness of clopidogrel. Clopidogrel and aspirin are often combined with a PPI to prevent gastrointestinal side effects. Gilard and colleagues studied the effect of omeprazole on clopidogrel therapy in patients following coronary artery stent therapy.

The Study: The authors conducted a prospective double-blind, placebo-controlled, randomized trial in patients undergoing elective coronary stent implantation. Patients with thrombocytopenia, bleeding disorders, hepatic disease, gastrointestinal ulcer, pregnancy, or previous use of PPIs or clopidogrel were excluded from the study. Following the initiation of treatment with aspirin (75 mg) and clopidogrel (300 mg loading dose followed by 75 mg per day), eligible patients were randomly assigned to receive omeprazole (20 mg per day) or an identical placebo for seven days. Blood tests for platelet reactivity index (PRI) were taken before the loading dose of clopidogrel and again after seven days of therapy. Higher PRI levels are associated with more frequent episodes of thrombosis during clopidogrel therapy. A PRI of less than 50 percent indicates a good response to clopidogrel, whereas a PRI of greater than 50 percent indicates a poor response.

Results: The 70 patients randomly assigned to receive omeprazole were similar to those assigned to receive placebo in all significant variables. Most participants were men (78 percent). The average age was approximately 63 years, and the majority of each group consisted of smokers. About 47 percent of the placebo group and 53 percent of the omeprazole group had hypertension. The mean PRI in the omeprazole group changed from 83.9 percent on the first day to 51.4 percent on the seventh day. In the placebo group, the mean PRI changed from 83.2 to 39.8 percent. The difference in effect between the two groups was statistically significant. In the omeprazole group, 39 patients (60.9 percent) were poor responders to clopidogrel, compared with 16 patients (26.7 percent) in the placebo group. The odds of being a poor responder were four times higher for patients in the omeprazole group.

Conclusion: The authors conclude that omeprazole significantly decreased the effect of clopidogrel on platelet function. They recommend not prescribing a PPI in combination with clopidogrel unless there are definitive indications. Because PPIs are commonly prescribed during aspirin and clopidogrel therapy to reduce the risk of gastrointestinal bleeding, this finding could have widespread clinical significance, and merits further research.

Source

Gilard M, et al. Influence of omeprazole on the antiplatelet action of clopidogrel associated with aspirin. J Am Col Cardiol. January 22, 2008;51(3):256-260.



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