The gain-of-function variant allele CYP2C19*17: a double-edged sword between thrombosis and bleeding in clopidogrel-treated patients
The gain-of-function variant allele CYP2C19*17: a double-edged sword between thrombosis and bleeding in clopidogrel-treated patients
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DOI：
10.1111/j.1538-7836.2011.04570.x
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发表时间：
2012-02-01
影响因子：
10.4
通讯作者：
Xie, H. -G.
中科院分区：
文献类型：
--
作者：
Li, Y.;Tang, H. -L.;Xie, H. -G.
。背景：大量临床研究证明，功能丧失变异体 CYP2C19*2 会影响氯吡格雷的临床特征（疗效和安全性）。然而，有关功能获得性变体 CYP2C19*17对该药物反应的影响的数据似乎不太一致。目的：系统总结评估 CYP2C19*17 变异在服用氯吡格雷患者中的作用的所有可用临床数据。方法：对 11 项符合条件的研究进行文献检索和荟萃分析。终点包括主要不良心血管事件（MACE，代表非致命性心肌梗塞、中风、血运重建或死亡）、出血事件、死亡率、支架内血栓形成和高血小板反应性（HPR）。结果：六项临床研究的数据表明，与非携带者相比，CYP2C19*17 变异携带者对冠状动脉疾病患者的复发性心血管事件具有显着保护作用，MACE 发生率降低 16%（10.0% vs. 11.9%；OR，0.82；95% CI，0.720.94；P = 0.005）。另一方面，正如预期的那样，携带者发生出血的风险增加（8.0% vs. 6.5%；OR，1.25；95% CI，1.071.47；P = 0.006；四项研究）。此外，CYP2C19*17 变异的存在可能会导致对氯吡格雷的反应增加，正如携带者中 HPR 患病率明显低于非携带者所表明的那样（37.9% vs. 50.8%；OR，0.60；95% CI，0.450.79；P = 0.0003；三项研究）。结论：CYP2C19*17 变异携带者对氯吡格雷的治疗反应性高于非携带者，但他们发生出血的风险也增加。
. Background: A large number of clinical studies have documented that a loss-of-function variant CYP2C19*2 affects clinical profiles of clopidogrel (efficacy and safety). However, data on the impact of a gain-of-function variant CYP2C19*17 on the response to that drug seem to be less consistent. Objectives: To systematically summarize all available clinical data assessing the role of the CYP2C19*17 variant in patients taking clopidogrel. Methods: A literature search was conducted and a meta-analysis was performed for 11 eligible studies. The endpoints included the major adverse cardiovascular events (MACE, representing non-fatal myocardial infarction, stroke, revascularization, or death), bleeding events, mortality, stent thrombosis and high platelet reactivity (HPR). Results: Data from six clinical studies demonstrated that carriers of the CYP2C19*17 variant had a marked protection against recurrent cardiovascular events in patients with coronary artery disease compared with non-carriers, as measured by a 16% decrease in the incidence of MACE (10.0% vs. 11.9%; OR, 0.82; 95% CI, 0.720.94; P = 0.005). On the other hand, carriers had an increased risk of developing bleeding as expected (8.0% vs. 6.5%; OR, 1.25; 95% CI, 1.071.47; P = 0.006; four studies). Moreover, the presence of the CYP2C19*17 variant might lead to increased response to clopidogrel, as shown by a marked lower prevalence of HPR in carriers than in non-carriers (37.9% vs. 50.8%; OR, 0.60; 95% CI, 0.450.79; P = 0.0003; three studies). Conclusions: Carriers of the CYP2C19*17 variant have greater therapeutic responsiveness to clopidogrel than non-carriers, but they have an increased risk of developing bleeding as well.