Effects of omeprazole on the antiplatelet activity of clopidogrel.
Clopidogrel is used with aspirin as a standard combined treatment in patients with acute coronary syndrome. A proton pump inhibitor (PPI) is often administered to patients receiving antiplatelet therapy. However, PPI use with clopidogrel was recently shown to result in increased risk of major cardiovascular events when compared to clopidogrel use alone. Therefore, the aim of the present study was to evaluate the effects of omeprazole, a PPI, on the antiplatelet effect of clopidogrel.We divided 20 healthy volunteers into 2 groups (n = 10 each). Twenty-four hours after a 300 mg loading dose of clopidogrel, one group received a dosage of 75 mg/day of clopidogrel and a placebo for 14 days, followed 3 weeks later by the same protocol but with coadministration of 75 mg/day clopidogrel and 20 mg/day omeprazole instead. The other group received the same treatment but in reverse order. Antiplatelet activity was assessed in terms of the P2Y12 reaction unit (PRU) and percentage inhibition using a VerifyNow P2Y12 assay system.The PRU of the omeprazole-treated subjects was significantly higher than that of the omeprazole-untreated subjects on day 14 (281.3 +/- 54.0 versus 240.0 +/- 72.2, P = 0.048). The percentage inhibition showed a decrease after the 14-day omeprazole treatment (22.7 +/- 29.9% versus 35.1 +/- 18.7%, P = 0.014). Consequently, omeprazole reduces the antiplatelet effect of clopidogrel, suggesting that careful treatment planning is required when administering omeprazole to patients on clopidogrel therapy.
Department of Cardiovascular Medicine, Wonkwang University Hospital.
Kyeong Ho
KH
Yun
Sang Jae
SJ
Rhee
Hyun-Young
HY
Park
Nam Jin
NJ
Yoo
Nam-Ho
NH
Kim
Seok Kyu
SK
Oh
Jin-Won
JW
Jeong
D000328:Adult; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D001792:Blood Platelets / Q000187:drug effects*; D000077144:Clopidogrel; D018592:Cross-Over Studies; D004347:Drug Interactions; D005260:Female; D006801:Humans; D008297:Male; D009853:Omeprazole / Q000494:pharmacology*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000494:pharmacology
D000897:Anti-Ulcer Agents; D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D009853:Omeprazole; D013988:Ticlopidine