21. PPIs reduces the antiplatelt effects of clopidogrel: According to a 2007 survey, clopidogrel is the sixth most commonly dispensed medication in the USA. To reduce the risk for gastrointestinal bleeding, clinicians often prescribe a concomitant proton-pump inhibitor (PPI) for high-risk patients. Recent evidence suggests that certain PPIs reduce the antiplatelet effects of clopidogrel. Clopidogrel, a prodrug, requires metabolism in the liver via cytochrome P450 (CYP) enzymes.

22. PPIs reduces the antiplatelt effects of clopidogrel: Proposed mechanism Once activated, clopidogrel blocks platelet aggregation by inhibiting adenosine diphosphate at the P2Y12 receptor. PPIs, such as omeprazole and its S-enantiomer esomeprazole (Nexium ® ), are thought to inhibit the CYP2C19 enzyme, thus negating the antithrombotic effects of clopidogrel. CYP2C19 also acts as the primary enzyme responsible for determining a patient’s pharmacodynamic response to clopidogrel.

26. PPIs reduces the antiplatelt effects of clopidogrel: Gilard and colleagues: Randomized, double-blind, placebo-controlled study. 145 patients undergoing PCI and receiving aspirin, 75 mg daily, and clopidogrel, 75 mg daily (after a 300-mg loading dose). 2 groups: The treatment group received omeprazole, 20 mg daily for 7 days, and the control group received placebo for 7 days. Assessment of the platelet reactivity index (PRI) was the primary endpoint. A PRI less than 50% indicated a favorable response to clopidogrel.

27. PPIs reduces the antiplatelt effects of clopidogrel: 145 patients undergoing PCI and receiving Aspirin, 75 mg daily, and clopidogrel, 75 mg daily (after a 300-mg loading dose). Pre-treatment: the PRI was 83.2% in the control group and 83.9% in the treatment group. Post-treatment: the PRI was 39.8% in the control group and 51.4% in the treatment group (P <.001). The long-term implications of this interaction are uncertain but may suggest reduced cardioprotective benefits of clopidogrel.