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使用三种不同的血小板功能测试来定义PCI术后维持双联抗血小板治疗中CYP2C19表型状态的预测值。

Defining predictive values using three different platelet function tests for CYP2C19 phenotype status on maintenance dual antiplatelet therapy after PCI.

作者信息

Zhang Hong-Zhe, Kim Moo Hyun, Han Jin-Yeong, Jeong Young-Hoon

机构信息

Department of Cardiology, Dong-A University Hospital , Busan , South Korea .

出版信息

Platelets. 2014;25(4):285-91. doi: 10.3109/09537104.2013.815340. Epub 2013 Aug 23.

Abstract

Published data suggests that the presence of CYP2C19*2 or *3 loss of function (LOF) alleles is indicative of increased platelet aggregation and a higher risk of adverse cardiovascular events after clopidogrel administration. We sought to determine cut-off values using three different assays for prediction of the CYP2C19 phenotype in Korean percutaneous coronary intervention (PCI) patients. We enrolled 244 patients with drug-eluting stent implantation who were receiving clopidogrel and aspirin maintenance therapy for one month or more. Platelet reactivity was assessed with light transmittance aggregometry (LTA), multiple electrode aggregometry (MEA) and the VerifyNow P2Y12 assay (VN). The CYP2C19 genotype was analyzed by polymerase chain reaction (PCR) and snapshot method. The frequency of CYP2C19 LOF allele carriers was 58.6%. The cut-off values from LTA, MEA and VerifyNow for the identification of LOF allele carriers were as follows: 10 µM ADP-induced LTA ≥ 48 %, VN>242 PRU and MEA ≥ 37 U. Between the three tests, correlation was higher between LTA vs. VN assays (r=0.69) and LTA vs. MEA (r=0.56), with moderate agreement (κ=0.46 and κ=0.46), but between VN assay and MEA, both devices using whole blood showed a lower correlation (r=0.42) and agreement (κ=0.3). Our results provide guidance regarding cut-off levels for LTA, VerifyNow and MEA assays to detect the CYP2C19 LOF allele in patients during dual antiplatelet maintenance therapy.

摘要

已发表的数据表明,CYP2C192或3功能缺失(LOF)等位基因的存在表明血小板聚集增加,以及服用氯吡格雷后发生不良心血管事件的风险更高。我们试图使用三种不同的检测方法来确定韩国经皮冠状动脉介入治疗(PCI)患者中CYP2C19表型预测的临界值。我们纳入了244例接受药物洗脱支架植入且接受氯吡格雷和阿司匹林维持治疗一个月或更长时间的患者。采用光透射聚集法(LTA)、多电极聚集法(MEA)和VerifyNow P2Y12检测法(VN)评估血小板反应性。通过聚合酶链反应(PCR)和快照法分析CYP2C19基因型。CYP2C19 LOF等位基因携带者的频率为58.6%。用于识别LOF等位基因携带者的LTA、MEA和VerifyNow的临界值如下:10µM ADP诱导的LTA≥48%,VN>242 PRU和MEA≥37 U。在这三种检测方法中,LTA与VN检测之间的相关性较高(r=0.69),LTA与MEA之间的相关性较高(r=0.56),一致性中等(κ=0.46和κ=0.46),但在VN检测和MEA之间,两种使用全血的设备显示出较低的相关性(r=0.42)和一致性(κ=0.3)。我们的结果为在双联抗血小板维持治疗期间检测患者中CYP2C19 LOF等位基因的LTA、VerifyNow和MEA检测方法临界水平提供了指导。

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