From the Division of Cardiology (M.D.K., G.A.S.).
Division of Pharmacotherapy and Experimental Therapeutics, Eshelman School of Pharmacy (A.K.W., C.R.L.).
Arterioscler Thromb Vasc Biol. 2019 Apr;39(4):647-652. doi: 10.1161/ATVBAHA.118.311963.
Current guidelines recommend dual antiplatelet therapy-a P2Y inhibitor (clopidogrel, prasugrel, or ticagrelor) and aspirin-for patients undergoing percutaneous coronary intervention. Although clopidogrel is the most commonly prescribed P2Y inhibitor, it is associated with an increased risk of major adverse cardiovascular events in patients carrying loss-of-function CYP2C19 alleles. In contrast, CYP2C19 genotype does not impact clinical response to prasugrel or ticagrelor. Nevertheless, routine implementation of CYP2C19 genotyping to guide antiplatelet therapy selection has remained controversial because of the lack of large randomized controlled trials evaluating this strategy. Emerging results from registry studies and small clinical trials of CYP2C19 genotype-guided antiplatelet therapy following percutaneous coronary intervention offer new insight and contribute to a growing evidence base that supports the clinical utility of a genotyping strategy to personalize antiplatelet therapy selection.
目前的指南建议接受经皮冠状动脉介入治疗的患者进行双联抗血小板治疗——一种 P2Y 抑制剂(氯吡格雷、普拉格雷或替格瑞洛)和阿司匹林。虽然氯吡格雷是最常开的 P2Y 抑制剂,但它与携带功能丧失 CYP2C19 等位基因的患者发生主要不良心血管事件的风险增加有关。相比之下,CYP2C19 基因型并不影响对普拉格雷或替格瑞洛的临床反应。然而,由于缺乏评估这种策略的大型随机对照试验,常规实施 CYP2C19 基因分型来指导抗血小板治疗选择一直存在争议。来自注册研究和经皮冠状动脉介入治疗后 CYP2C19 基因分型指导抗血小板治疗的小型临床试验的新结果提供了新的见解,并为支持基因分型策略个性化抗血小板治疗选择的临床实用性的不断增长的证据基础做出了贡献。