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 .

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.

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 .