Resistance to clopidogrel: A review of the evidence

被引:429
作者
Nguyen, TA
Diodati, JG
Pharand, C
机构
[1] Hop Sacre Coeur, Res Ctr, Montreal, PQ H4J 1C5, Canada
[2] Hop Sacre Coeur, Dept Pharm, Montreal, PQ H4J 1C5, Canada
[3] Hop Sacre Coeur, Serv Cardiol, Montreal, PQ H4J 1C5, Canada
[4] Univ Montreal, Fac Pharm, Montreal, PQ H3C 3J7, Canada
[5] Univ Montreal, Fac Med, Montreal, PQ H3C 3J7, Canada
关键词
D O I
10.1016/j.jacc.2005.01.034
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Current available data show that about 4% to 30% of patients treated with conventional doses of clopidogrel do not display adequate antiplatelet response. Clopidogrel resistance is a widely used term that remains to be clearly defined. So far, it has been used to reflect failure of clopidogrel to achieve its antiaggregatory effect. The interpatient variability in clopidogrel response is multifactorial. It can be due to extrinsic or intrinsic mechanisms. Among extrinsic mechanisms are the possibility of clopidogrel underdosing in patients undergoing stenting or with acute coronary syndrome, and drug-drug interactions involving CYP3A4. Intrinsic mechanisms include genetic polymorphisms of the P2Y(12) receptor and of the CYP3As, accrued release of adenosine diphosphate, or up-regulation of other platelet activation pathways. Presently, there is no definite demonstration of an association between low responsiveness to clopidogrel and thrombotic events. The optimal level of clopidogrel-induced platelet inhibition, which will correlate quantitatively with clopidogrel's ability to prevent atherothrombotic events is still lacking. Furthermore, because there is no single and validated platelet function assay to measure clopidogrel's antiplatelet effect, it is not justified to routinely look for clopidogrel resistance in the clinical setting. This review discusses currently available evidence surrounding the variability in the antiplatelet response to clopidogrel.
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页码:1157 / 1164
页数:8
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