Dissertation
Dissertation > Medicine, health > Internal Medicine > Heart, blood vessels ( circulatory ) disease > Heart disease > Coronary arteries ( atherosclerosis ),heart disease (CHD)

The Research of Impact of Proton Pump Inhibitor Omeprazole on the Antiplatelet Effects of Clopidogrel

Author ZuoZiLian
Tutor XuJing
School Tianjin Medical University
Course Internal Medicine
Keywords acute coronary syndrome clopidogrel omeprazole cimetidine cytochrome P450 CYP2C19 gene mutation
CLC R541.4
Type Master's thesis
Year 2011
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Purpose:Patients receiving dual antiplatelet treatment with aspirin and clopidogrel are commonly treated with proton pump inhibitors (PPIs). Attenuating effects on platelet response to clopidogrel have been reported solely for the PPI omeprazole. The aim of this study was to compare the impact of omeprazole on platelet response to clopidogrel in patients with percutaneous coronary intervention (PCI) under clopidogrel treatment with the impatct of H2 receptor antagonist cimetidine. The effect of polymorphisms of CYP2C19 on the antiplatelet effect of clopidogrel in clinical patients was examined in the present study.Method:The study population included 309 patients with acute coronary syndrome (ACS) undergoing PCI. Adenosine diphosphate (ADP)-induced -platelet aggregation (PA) were assessed before 300mg aspirin plus 300mg loading dose of clopidogrel and after 300mg asprin plus 75mg maintenance dose of clopidogrel 7days later.Then the gastric mucosal protective drugs were given (omeprazolem20mg,n=174 and cimetidine800mg. N=135).14 days later, PA were tested again and inhibition of platelet aggregation (PAI)was calculated. The CYP2C19*2 and CYP2C19*3 genotypes were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).Results:After taken aspirin and clopidogrel, the PA decreased significantly in both group. Compared with cimetidine, omeprazole had no significant effect on PA and PAI in post PCI 7days and post PCI 21 days. The rate of CYP2C19*2 variant is higer than that of CYP2C19*3 variant(17.8% vs 0.18%).Compared with the patients carried with CYP2C19*2 wild-type and heterozygous type, the CYP2C19*2 variant carriage patient had higher PA in post-PCI 7days and post-PCI 21 days and lower PAI in post-PCI 21 days. The PA and PAI of three genotypes of CYP2C19*3 carriage had no significant difference.Conclusion: No attenuating effects on platelet response to clopidogrel were observed for Omeprazole.The variant of CYP2C19* 2 is more common.The variant of CYP2C19* 2 carrier is significantly associated with attenuated response to clopidogrelThe three genotype of CYP2C19* 3 didn’t effect the function of clopidogrel.

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