Background: Clopidogrel (Plavix) is used incombination with aspirin in the preventionof atherothrombotic conditions, especiallyfollowing placement of stents. Activationof clopidogrel requires several steps, mediatedmainly by cytochrome P450 isoenzymes.Because one of these isoenzymes, CYP2C19,is also involved in the metabolism of protonpump inhibitors (PPIs), the use of PPIssuch as omeprazole (Prilosec) could reducethe biologic effectiveness of clopidogrel.Clopidogrel and aspirin are often combinedwith a PPI to prevent gastrointestinal sideeffects. Gilard and colleagues studied theeffect of omeprazole on clopidogrel therapyin patients following coronary artery stenttherapy.

The Study: The authors conducted a prospectivedouble-blind, placebo-controlled,randomized trial in patients undergoingelective coronary stent implantation.Patients with thrombocytopenia, bleedingdisorders, hepatic disease, gastrointestinalulcer, pregnancy, or previous use of PPIs orclopidogrel were excluded from the study. Followingthe initiation of treatment with aspirin(75 mg) and clopidogrel (300 mg loadingdose followed by 75 mg per day), eligiblepatients were randomly assigned to receiveomeprazole (20 mg per day) or an identicalplacebo for seven days. Blood tests for plateletreactivity index (PRI) were taken beforethe loading dose of clopidogrel and againafter seven days of therapy. Higher PRI levelsare associated with more frequent episodesof thrombosis during clopidogrel therapy.A PRI of less than 50 percent indicates agood response to clopidogrel, whereas a PRIof greater than 50 percent indicates a poorresponse.

Results: The 70 patients randomly assignedto receive omeprazole were similar to thoseassigned to receive placebo in all significantvariables. Most participants were men(78 percent). The average age was approximately63 years, and the majority of eachgroup consisted of smokers. About 47 percentof the placebo group and 53 percentof the omeprazole group had hypertension.The mean PRI in the omeprazole groupchanged from 83.9 percent on the first day to51.4 percent on the seventh day. In the placebogroup, the mean PRI changed from83.2 to 39.8 percent. The difference in effectbetween 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 beinga poor responder were four times higher forpatients in the omeprazole group.

Conclusion: The authors conclude thatomeprazole significantly decreased theeffect of clopidogrel on platelet function.They recommend not prescribing a PPI incombination with clopidogrel unless thereare definitive indications. Because PPIs arecommonly prescribed during aspirin andclopidogrel therapy to reduce the risk of gastrointestinalbleeding, this finding could havewidespread clinical significance, and meritsfurther research.