Zeb Irfan, Krim Nassim, Bella Jonathan
a Division of Cardiology, Department of Medicine , Bronxcare Health System , Bronx , NY , USA.
b Division of Cardiology, Department of Medicine , Icahn School of Medicine at Mount Sinai , New York , NY , USA.
Expert Rev Cardiovasc Ther. 2018 May;16(5):369-377. doi: 10.1080/14779072.2018.1459186. Epub 2018 Apr 3.
P2Y12 inhibitors, including clopidogrel have become an integral part of treatment for patients receiving coronary stent placement as a result of stable coronary artery disease or acute coronary syndromes (ACS) and also for medically managed ACS patients. Areas covered: Clopidogrel efficacy can be significantly modified by polymorphism of CYP2C19 genotype (more than 25 allelic variants) involved in its metabolism that can adversely affect its anti-platelet activity. As a result, a substantial number of patients (20-30%) with ACS show an inadequate response to clopidogrel despite a standardized dosing regimen. Experts commentary: Currently, there is conflicting evidence in regards to the use of CYP2C19 genotyping to identify poor responders to clopidogrel in clinical practice. ACC/AHA guidelines do not recommend routine use of CYP2C19 in clinical practice, whereas Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines recommend its use to identify poor/intermediate metabolizers of Clopidogrel and suggest alternative P2Y12 inhibitors among ACS patients undergoing percutaneous coronary intervention. This review article will look at the literature evidence for the use of CYP2C19 genotyping in clinical practice.
P2Y12抑制剂,包括氯吡格雷,已成为因稳定型冠状动脉疾病或急性冠状动脉综合征(ACS)接受冠状动脉支架置入术患者以及接受药物治疗的ACS患者治疗中不可或缺的一部分。涵盖领域:氯吡格雷的疗效可因参与其代谢的CYP2C19基因多态性(超过25种等位基因变体)而显著改变,这可能对其抗血小板活性产生不利影响。因此,相当一部分(20%-30%)ACS患者尽管采用了标准化给药方案,但对氯吡格雷的反应仍不充分。专家评论:目前,关于在临床实践中使用CYP2C19基因分型来识别氯吡格雷反应不佳者,存在相互矛盾的证据。美国心脏病学会/美国心脏协会(ACC/AHA)指南不建议在临床实践中常规使用CYP2C19基因分型,而临床药物基因组学实施联盟(CPIC)指南则建议使用该基因分型来识别氯吡格雷的慢代谢/中代谢者,并建议在接受经皮冠状动脉介入治疗的ACS患者中使用替代P2Y12抑制剂。这篇综述文章将探讨在临床实践中使用CYP2C19基因分型的文献证据。