Impact of clopidogrel resistance on thrombotic events after percutaneous coronary intervention with drug-eluting stent

Wang, Zhi Jian; Zhou, Yu Jie; Liu, Yu Yang; Ming, Yu; Shi, Dong; Zhao, Ying; Guo, Yong; Cheng, Wan Jun; Jia, De An; Cao, Zheng; Nie, Bin; Ge, Hai; Yang, Shi Wei; Yan, Zhen

doi:10.1016/j.thromres.2008.10.007

Cited by 37 publications

(30 citation statements)

References 44 publications

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“…[4][5][6][7] Small-scale investigations have suggested that clopidogrel resistance may be associated with a heightened risk of adverse clinical events. [13][14][15][16] The mechanisms underlying clopidogrel resistance are still controversial. Possible mechanisms include drug interaction involving the cytochrome P450 enzyme, insulin resistance, poor bioavailability, and polymorphisms of the cytochrome P450 3A and P2Y12 receptor genes.…”

Section: Discussionmentioning

confidence: 99%

Effects of Omeprazole on the Antiplatelet Activity of Clopidogrel

et al. 2010

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SummaryClopidogrel 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. (Int Heart J 2010; 51: 13-16) Key words: Platelet, Clopidogrel, Omeprazole, Drug resistance T he use of powerful antiplatelet agents is increasing as drug-eluting stents (DES) become more widely used. Clopidogrel is used with aspirin as a standard combined treatment for secondary prevention of acute coronary syndrome and prevention of stent thrombosis in patients with coronary stents.1-3) Despite its proven benefit, the individual patient responses to clopidogrel show considerable heterogeneity. Recent data show that an adequate antiplatelet effect is not achieved in 4 -30% of the patients on clopidogrel, suggesting that many patients are resistant or only partially responsive to the antiplatelet effect of the drug. 4-7)A number of different factors may influence the antiplatelet effect of clopidogrel. Drug interaction could be one important factor. Clopidogrel is an inactive prodrug that requires in vivo conversion to an active metabolite by the cytochrome P450 3A4 enzyme system in the liver. 8,9) Therefore, the drug component that involves the cytochrome P450 enzyme system may be the cause of clopidogrel resistance. A proton pump inhibitor (PPI) is often administered to patients receiving antiplatelet therapy for treating gastrointestinal symptoms or bleeding. However, results from a recent large population-based study have suggested that PPI use with clopidogrel results in increased risk of major cardiovascular events as compared to clopidogrel use alone. 10)In this study, to evaluate the interaction between...

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Section: Discussionmentioning

confidence: 99%

Effects of Omeprazole on the Antiplatelet Activity of Clopidogrel

et al. 2010

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“…Although interruption of antiplatelet therapy may explain the occurrences of late and very late ST, it does not explain occurrences of acute and subacute ST on treatment as current clinical practice dictates the use of aspirin indefinitely and clopidogrel for ≥1 month following PCI depending on whether a bare-metal or drug-eluting stent is used [13]. More recently investigators have suggested that reduced platelet inhibition by aspirin and thienopyridines can be seen as a potential contributor to this phenomenon [14][15][16]. From a clinical perspective, several key questions require further clarification.…”

Section: And 41% [3-7] and Leads To Significant Clinical Complicatiomentioning

confidence: 99%

High on Treatment Platelet Reactivity and Stent Thrombosis

Rajendran¹,

Parikh

Shugman³

et al. 2011

Heart, Lung and Circulation

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“…Numerous studies using different platelet function tests have noted estimates of clopidogrel resistance ranging from 16.8e21%. 16,17 However, because of the many drawbacks of each platelet function test, none of the currently available tests, including platelet aggregometry and the Platelet Function Anaylzer-100 test (Dade Behring, Deerfield, IL) can be recommended for clinical practice. 18 Because of the limitations in funding, clopidogrel resistance was not tested in this study.…”

Section: Discussionmentioning

confidence: 99%