氯吡格雷抵抗的药物基因组学研究进展

Pharmacogenomics of Clopidogrel Resistance

目前,氯吡格雷联合阿司匹林双重抗血小板是治疗急性冠状动脉综合征和经皮冠状动脉介入术后抗栓的基础药物。然而,氯吡格雷抗血小板作用的反应存在个体差异,氯吡格雷抵抗现象日益受到关注。但氯吡格雷抵抗的机制仍不完全清楚,明确抵抗的原因和机制将使冠状动脉疾病患者受益匪浅。现就氯吡格雷抵抗的定义、检测方法、可能机制及药物基因组学进行综述。

Across the spectrum of acute coronary syndromes and in patients undergoing percutaneous coronary interventions （PCI） with stenting, dual antiplatelet therapy with aspirin and clopidogrel is the standard of care. However, the pharmacodynamic response to clopidogrel has substantial interpatient variability. Clopidogrel resistance is emerging clinical problem with potentially severe consequences such as recurrent myocardial infarction, stroke, or death. The mechanism of resistance remains incompletely understood, but there are specific clinical, cellular, and genetic factors that influence therapeutic failure. By understanding the mechanism of therapeutic failure and by improving the diagnosis of this clinical entity, a new era of individualized antiplatelet therapy may arise with routine measurements of platelet activity in the same way that cholesterol, blood pressure, and blood sugar are followed, thus improving the care for millions of people. At present, we review the definition, tests, possible mechanism and pharmacogenomics of clopidogrel resistance.