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CYP2C19 基因分型联合氯吡格雷抵抗血小板反应性预测中国经皮冠状动脉介入治疗患者的主要不良心血管事件。

CYP2C19 genotyping combined with on-clopidogrel platelet reactivity in predicting major adverse cardiovascular events in Chinese patients with percutaneous coronary intervention.

机构信息

State Key Laboratory of Cardiovascular Disease, Department of Cardiology, Centre for Coronary Heart Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, China.

Department of Cardiology, Institute of Cardiovascular Research of People's Liberation Army, Shenyang Northern Hospital, Shenyang, Liaoning 110840, China.

出版信息

Thromb Res. 2016 Nov;147:108-114. doi: 10.1016/j.thromres.2016.10.008. Epub 2016 Oct 7.

Abstract

INTRODUCTION

Both CYP2C19 genotyping and platelet function testing are used to predict major adverse cardiac events (MACEs) in Chinese patients treated with clopidogrel and undergoing stent implantation, but the most accurate prognostic technique is still debated. Here, we combine both techniques, to determine if a more accurate prognosis is possible.

METHODS

Patients undergoing stent implantation (1104) were genotyped and assessed for platelet reactivity, with a 12-month follow-up. The CYP2C19*2 (rs4244285), and *3 (rs4986893) alleles were genotyped. High on treatment platelet reactivity was defined as adenosine diphosphate (ADP)-induced platelet inhibition ≤30%. MACEs included death, nonfatal myocardial infarction, target vessel revascularization, or stent thrombosis.

RESULTS AND CONCLUSIONS

Hazard ratios (HRs) for cardiovascular ischemic outcomes based on the two testing methods are as follows. CYP2C19 genotyping: carriers of CYP2C19 loss-of-function alleles, HR: 2.515, 95% confidence interval (CI), 1.150-5.501, P=0.021; ADP-induced platelet inhibition ≤30%, HR: 1.992, 95% CI, 1.040-3.818, P=0.038. An ischemic risk score between zero and two was calculated. Compared with the group with a score of zero, HRs for adverse cardiovascular outcomes were 4.078 for those with a score of two (95% CI: 1.525-10.905, P=0.005). However, there was no significant difference between the group with the score of zero and the group with the score of one. CYP2C19 genotyping combined with platelet reactivity is an independent and additive predictor of 1-year MACE in Chinese patients undergoing stenting with clopidogrel treatment, which is better than either test alone.

摘要

简介

CYP2C19 基因分型和血小板功能检测均用于预测接受氯吡格雷治疗和支架植入的中国患者的主要不良心脏事件(MACEs),但最准确的预测技术仍存在争议。在这里,我们将这两种技术结合起来,以确定是否可以获得更准确的预后。

方法

对 1104 例接受支架植入术的患者进行基因分型和血小板反应性评估,并进行 12 个月的随访。检测 CYP2C192(rs4244285)和3(rs4986893)等位基因。ADP 诱导的血小板抑制率≤30%定义为高治疗血小板反应性。MACE 包括死亡、非致死性心肌梗死、靶血管血运重建或支架血栓形成。

结果与结论

基于两种检测方法的心血管缺血性结局的危险比(HRs)如下。CYP2C19 基因分型:CYP2C19 失活等位基因携带者,HR:2.515,95%置信区间(CI)为 1.150-5.501,P=0.021;ADP 诱导的血小板抑制率≤30%,HR:1.992,95%CI 为 1.040-3.818,P=0.038。计算缺血风险评分从 0 到 2。与评分 0 的组相比,评分 2 的组不良心血管结局的 HR 为 4.078(95%CI:1.525-10.905,P=0.005)。然而,评分 0 与评分 1 的组之间没有显著差异。CYP2C19 基因分型结合血小板反应性是接受氯吡格雷治疗的中国患者支架置入后 1 年 MACE 的独立且附加预测因子,优于单独任何一种检测。

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