035 Comparison of Omeprazole and Pantoprazole Influence on Clopidogrel Effect of a High 150 mg Maintenance Dose: the Proton pomp inhibitors and Clopidogrel Association (PACA) prospective, randomized study

Changing Prescription Pattern of Omeprazole Among Patients Receiving Clopidogrel

“…2,3) Some of the studies confirmed an interaction between clopidogrel and PPI. 4,5,[8][9][10] Kyeong, et al found that the P2Y12 reaction unit (PRU) of omeprazole treated subjects was signifi cantly higher than that of the omeprazole untreated subjects and the percentage inhibition decreased in the omeprazole treatment versus no omeprazole treatment. 4) Moreover, it has been found that patients taking clopidogrel plus a PPI had a higher risk of hospitalization for recurrent acute coronary syndrome compared with patients taking clopidogrel without a PPI.…”

“…[1][2][3] However, the mechanisms underlying this variability remain controversial and multiple factors seem to be involved. [4][5][6] These include drug interactions involving the cytochrome P450 (CYP450), insulin resistance, poor bioavailability, and polymorphisms of the CYP450 and P2Y12 receptor genes. 4,5) Proton pump inhibitors (PPI) are usually given to patients receiving antiplatelet therapy to prevent gastrointestinal symptoms and are metabolized mainly by the CYP450.…”

“…[4][5][6] These include drug interactions involving the cytochrome P450 (CYP450), insulin resistance, poor bioavailability, and polymorphisms of the CYP450 and P2Y12 receptor genes. 4,5) Proton pump inhibitors (PPI) are usually given to patients receiving antiplatelet therapy to prevent gastrointestinal symptoms and are metabolized mainly by the CYP450. 1,7) Different observational studies showed significant cardiovascular adverse events arising from a potential drug interaction due to concomitant use of clopidogrel and PPIs.…”

“…1,7) Different observational studies showed significant cardiovascular adverse events arising from a potential drug interaction due to concomitant use of clopidogrel and PPIs. 1,4,5,[8][9][10] The inhibitory effect of omeprazole on the antiaggregation effects of clopidogrel is most pronounced among the various PPIs studied.…”

The prophylactic use of a proton pump inhibitor (PPI) in patients treated with clopidogrel and aspirin for an acute coronary syndrome or placement of a coronary stent reduces the rate of upper gastrointestinal bleeding with no apparent increase in cardiovascular events

“…Clopidogrel is a prodrug converted in the liver to its active form by cytochrome P450 isoenzymes, with the CYP450 isoform 2C19 playing a major role in this metabolism. There is evidence suggesting that various PPIs, and most consistently omeprazole [4] can inhibit CYP2C19, which alters the effectiveness of clopidogrel, and potentially leads to an increased risk of adverse cardiovascular outcomes.…”