表型分析与基因分型预测氯吡格雷疗效和安全性：PEGASUS-PCI 研究。
Phenotyping vs. genotyping for prediction of clopidogrel efficacy and safety: the PEGASUS-PCI study.
机构信息
Department of Cardiology, Medical University of Vienna, Vienna, Austria.
出版信息
J Thromb Haemost. 2012 Apr;10(4):529-42. doi: 10.1111/j.1538-7836.2012.04639.x.
BACKGROUND
Prognostic values of genotyping and phenotyping for assessment of clopidogrel responsiveness have been shown in independent studies.
OBJECTIVES
To compare different assays for prediction of events during long-term follow-up.
METHODS
In this prospective cohort study polymorphisms of CYP2C192 and CYP2C1917 alleles, vasodilator-stimulated phosphoprotein phosphorylation (VASP) assay, multiple electrode aggregometry (MEA), cone and platelet analyser (CPA) and platelet function analyser (PFA-100) were performed in 416 patients undergoing percutaneous coronary intervention. The rates of events were recorded during a 12-month follow-up.
RESULTS
Platelet aggregation by MEA predicted stent thrombosis (2.4%) better (c-index = 0.90; P < 0.001; sensitivity = 90%; specificity = 83%) than the VASP assay, CPA or PFA-100 (c-index < 0.70; P > 0.05; sensitivity < 70%; specificity < 70% for all) or even the CYP2C192 polymorphism (c-index < 0.56; P > 0.05; sensitivity = 30%; specificity = 71%). Survival analysis indicated that patients classified as poor responders by MEA had a substantially higher risk of developing stent thrombosis or MACE than clopidogrel responders (12.5% vs. 0.3%, P < 0.001, and 18.5% vs. 11.3%, P = 0.022, respectively), whereas poor metabolizers (CYP2C19*1/*2 or *2/*2 carriers) were not at increased risks (stent thrombosis, 2.7% vs. 2.5%, P > 0.05; MACE, 13.5% vs. 12.1%, P = 0.556). The incidence of major bleedings (2.6%) was numerically higher in patients with an enhanced vs. poor response to clopidogrel assessed by MEA (4% vs. 0%) or in ultra-metabolizers vs. regular metabolizers (CYP2C1917/17 vs. CYP2C191/*1; 9.5% vs. 2%). The classification tree analysis demonstrated that acute coronary syndrome at hospitalization and diabetes mellitus were the best discriminators for clopidogrel responder status.
CONCLUSIONS
Phenotyping of platelet response to clopidogrel was a better predictor of stent thrombosis than genotyping.
背景
已有独立研究表明，基因分型和表型分析对于评估氯吡格雷反应性的预后价值。
目的
比较不同检测方法在长期随访中预测事件的能力。
方法
本前瞻性队列研究对 416 例行经皮冠状动脉介入治疗的患者进行了 CYP2C192 和 CYP2C1917 等位基因、血管扩张刺激磷蛋白磷酸化（VASP）检测、多电极聚集检测（MEA）、锥形血小板分析仪（CPA）和血小板功能分析仪（PFA-100）检测。在 12 个月的随访期间记录事件发生率。
结果
MEA 检测的血小板聚集预测支架血栓形成（2.4%）的能力优于 VASP 检测、CPA 或 PFA-100（c 指数<0.70；P>0.05；敏感性<70%；特异性<70%），甚至优于 CYP2C192 多态性（c 指数<0.56；P>0.05；敏感性 30%；特异性 71%）。生存分析表明，MEA 检测的反应不良患者发生支架血栓形成或主要不良心血管事件的风险显著高于氯吡格雷反应良好的患者（12.5% vs. 0.3%，P<0.001；18.5% vs. 11.3%，P=0.022），而代谢不良（CYP2C19*1/*2 或 *2/*2 携带者）患者的风险未增加（支架血栓形成 2.7% vs. 2.5%，P>0.05；MACE 13.5% vs. 12.1%，P=0.556）。MEA 检测氯吡格雷反应增强的患者（4% vs. 0%）或超代谢者（CYP2C1917/17 与 CYP2C191/*1）的主要出血发生率（2.6%）高于氯吡格雷反应不良的患者（9.5% vs. 2%）。分类树分析表明，住院时的急性冠状动脉综合征和糖尿病是预测氯吡格雷反应者状态的最佳判别因素。
结论
氯吡格雷反应的表型分析是支架血栓形成的更好预测指标，优于基因分型。
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