关于患有心肌梗死后接受氯吡格雷治疗的年轻患者细胞色素P450 2C19多形态性的队列研究

发布于:2009-02-10 08:48

关于患有心肌梗死后接受氯吡格雷治疗的年轻患者细胞色素P450 2C19多形态性的队列研究

背景

氯吡格雷和低剂量阿斯匹林已经成为急性冠脉综合征或支架置入后防止再发局部缺血事件的主要口服抗血小板药物。频繁发生功能变异681 G>A (*2)的细胞色素P450 2C19 (CYP2C19)是氯吡格雷抗血小板效果个体间差异性大的重要因素。研究者评价了CYP2C19*2的多形态性是否影响长期应用氯吡格雷治疗患者的远期预后。

方法

1996.4.1-2008.4.1，259名首次发生心肌梗死（年龄<45岁）并且应用氯吡格雷治疗至少一个月的年轻患者，入选多中心登记注册并检测CYP2C19*2。主要终点包括应用氯吡格雷过程中出现死亡，心肌梗死和急性冠脉搭桥手术。每6个月随访一次。关键次要终点是血管造影后诊断出现血栓。

结果

中位氯吡格雷治疗时间为1.07年(IQR 0.28—3.0)。

基线特征是在CYP2C19*2变异体的载体（杂合子*1/*2, n=64；纯合子*2/*2, n=9)和非载体（n=186）间保持平衡。主要终点在载体组比非载体组出现更频繁（15 vs.11事件；危害比率3.69[95% CI 1.69—8.05]，p=0.0005)，和支架血栓一样（8 vs.4事件；HR 6.02 [1.81—20.04], p=0.0009)。

CYP2C19*2基因变异的危害作用在氯吡格雷开始应用直至随访结束持续6个月(HR 3•00 [1.27—7.10], p=0.009)。在多变量分析后，，CYP2C19*2基因变异体是唯一的心血管事件的单独预测因子(HR 4.04 [1.81—9.02], p=0.0006)。

名词解释

CYP2C19*2基因变异是一个在心肌梗死后接受氯吡格雷治疗的年轻患者预后的主要决定因素。

Source:www.thelancet.com

《医心评论》编辑：呼唤翻译毛新罡校对

Cytochrome P450 2C19 polymorphism in young patients treated with clopidogrel after myocardial infarction: a cohort study

Background

Clopidogrel and low-dose aspirin have become the mainstay oral antiplatelet regimen to prevent recurrent ischaemic events after acute coronary syndromes or stent placement. The frequent genetic functional variant 681 G>A (*2) of cytochrome P4502C19 (CYP2C19) is an important contributor to the wide variability between individuals of the antiplatelet effect of clopidogrel. We assessed whether the CYP2C19*2 polymorphism affected long-term prognosis of patients who were chronically treated with clopidogrel.

Methods

Between April 1, 1996, and April 1, 2008, 259 young patients (aged <45 years) who survived a first myocardial infarction and were exposed to clopidogrel treatment for at least a month, were enrolled in a multicentre registry and underwent CYP2C19*2 determination. The primary endpoint was a composite of death, myocardial infarction, and urgent coronary revascularisation occurring during exposure to clopidogrel. Follow-up was every 6 months. The key secondary endpoint was stent thrombosis proven by angiography.

Findings

Median clopidogrel exposure time was 1·07 years (IQR 0·28—3·0). Baseline characteristics were balanced between carriers (heterozygous *1/*2, n=64; homozygous *2/*2, n=9) and non-carriers (n=186) of CYP2C19*2 variant. The primary endpoint occurred more frequently in carriers than in non-carriers (15 vs 11 events; hazard ratio [HR] 3·69 [95% CI 1·69—8·05], p=0·0005), as did stent thrombosis (eight vs four events; HR 6·02 [1·81—20·04], p=0·0009).

The detrimental effect of the CYP2C19*2 genetic variant persisted from 6 months after clopidogrel initiation up to the end of follow-up (HR 3·00 [1·27—7·10], p=0·009). After multivariable analysis, the CYP2C19*2 genetic variant was the only independent predictor of cardiovascular events (HR 4·04 [1·81—9·02], p=0·0006).

Interpretation

The CYP2C19*2 genetic variant is a major determinant of prognosis in young patients who are receiving clopidogrel treatment after myocardial infarction.

来源：医心网

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