Reduced-function CYP2C19 genotype and risk of adverse clinical outcomes among patients treated with clopidogrel predominantly for PCI: a meta-analysis.
Reduced-function CYP2C19 genotype and risk of adverse clinical outcomes among patients treated with clopidogrel predominantly for PCI: a meta-analysis.
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降低功能的CYP2C19基因型和氯吡格雷治疗的患者中主要患有PCI的患者的不良临床结局的风险：一项荟萃分析。
DOI：
10.1001/jama.2010.1543
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发表时间：
2010-10-27
期刊：
影响因子：
--
通讯作者：
Sabatine MS
中科院分区：
文献类型：
--
作者：
Mega JL;Simon T;Collet JP;Anderson JL;Antman EM;Bliden K;Cannon CP;Danchin N;Giusti B;Gurbel P;Horne BD;Hulot JS;Kastrati A;Montalescot G;Neumann FJ;Shen L;Sibbing D;Steg PG;Trenk D;Wiviott SD;Sabatine MS
氯吡格雷是最常用的处方药之一，是一种需要CYP 450生物转化的前药。数据表明，其药理作用因CYP 2C 19基因型而异，但特定基因型带来的临床风险尚不确定。在接受氯吡格雷治疗的患者中，确定一种功能降低的CYP 2C 19变体携带者（白人患病率为26%）和两种功能降低的CYP 2C 19变体携带者（白人患病率为22%）发生主要不良心血管结局的风险。对MEDLINE、科克伦和EMBASE数据库进行了文献检索（2000年1月至2010年8月）。纳入了遗传学研究，其中以符合当前指南建议的方式在主要采用侵入性管理的患者中开始使用氯吡格雷，并确定了临床结局。来自9项评估接受氯吡格雷治疗患者的CYP 2C 19基因型和临床结局的研究的研究者提供了按基因型划分的特定心血管结局的相关风险比（HR）及其95%置信区间（CI）。在9685例患者中[91.3%接受了经皮冠状动脉介入治疗（PCI），54.5%患有急性冠状动脉综合征（ACS）]，863例发生了心血管死亡、心肌梗死或卒中的复合终点;在5894例接受此类评价的患者中，84例发生了支架内血栓形成。总体而言，71.5%为非携带者，26.3%有一个，2.2%有两个CYP 2C 19功能降低的等位基因。复合终点的风险显著增加在一个（HR 1.55，95% CI 1.11-2.27，P=0.01）和两个（HR 1.76，95% CI 1.24-2.50，P=0.002）CYP 2C 19功能降低等位基因的携带者中是明显的。同样，在携带1个（HR 2.67，95% CI 1.69-4.22，P<0.0001）和2个（HR 3.97，95% CI 1.75-9.02，P=0.001）CYP 2C 19功能降低等位基因的患者中，支架内血栓形成的风险显著增加。在接受氯吡格雷PCI治疗的患者中，即使携带一个功能降低的CYP 2C 19等位基因，似乎也与主要不良心血管事件（特别是支架血栓形成）的风险显著增加相关。
Clopidogrel, one of the most commonly prescribed medications, is a pro-drug requiring CYP450 biotransformation. Data suggest its pharmacologic effect varies based on CYP2C19 genotype, but there is uncertainty regarding the clinical risk imparted by specific genotypes. In patients treated with clopidogrel, to define the risk of major adverse cardiovascular outcomes among carriers of one (∼26% prevalence in whites) and carriers of two (∼2% prevalence in whites) reduced-function CYP2C19 variants. A literature search was conducted (January 2000-August 2010) of the MEDLINE, Cochrane, and EMBASE databases. Genetic studies were included where clopidogrel was initiated in predominantly invasively managed patients in a manner consistent with the current guideline recommendations and where clinical outcomes were ascertained. Investigators from nine studies evaluating CYP2C19 genotype and clinical outcomes in patients treated with clopidogrel contributed the relevant hazard ratios (HRs) and their 95% confidence intervals (CI) for specific cardiovascular outcomes by genotype. Among 9685 patients [91.3% of whom underwent percutaneous coronary intervention (PCI) and 54.5% of whom had an acute coronary syndrome (ACS)], 863 experienced the composite endpoint of cardiovascular death, myocardial infarction, or stroke; 84 patients had stent thrombosis among the 5894 evaluated for such. Overall, 71.5% were non-carriers, 26.3% had one, and 2.2% had two CYP2C19 reduced-function alleles. A significantly increased risk of the composite endpoint was evident in both carriers of one (HR 1.55, 95% CI 1.11-2.27, P=0.01) and two (HR 1.76, 95% CI 1.24-2.50, P=0.002) CYP2C19 reduced-function alleles. Similarly, there was a significantly increased risk of stent thrombosis in both carriers of one (HR 2.67, 95% CI 1.69-4.22, P<0.0001) and two (HR 3.97, 95% CI 1.75-9.02, P=0.001) CYP2C19 reduced-function alleles. Among patients treated with clopidogrel for PCI, carriage of even one reduced-function CYP2C19 allele appears to be associated with a significantly increased risk of major adverse cardiovascular events, particularly stent thrombosis.
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影响因子：
120.7
作者：
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