Prospective Evaluation of On-Clopidogrel Platelet Reactivity Over Time in Patients Treated With Percutaneous Coronary Intervention Relationship With Gene Polymorphisms and Clinical Outcome
Prospective Evaluation of On-Clopidogrel Platelet Reactivity Over Time in Patients Treated With Percutaneous Coronary Intervention Relationship With Gene Polymorphisms and Clinical Outcome
复制标题
DOI：
10.1016/j.jacc.2010.12.047
复制
发表时间：
2011-06-21
影响因子：
24
通讯作者：
Valgimigli, Marco
中科院分区：
文献类型：
--
作者：
Campo, Gianluca;Parrinello, Giovanni;Valgimigli, Marco
目的本研究旨在探讨经皮冠状动脉介入治疗后，氯吡格雷治疗后血小板反应性（PR）随时间的变化模式及其与基因型和临床结局的关系。背景：经皮冠状动脉介入治疗前，以及经皮冠状动脉介入治疗后1个月和6个月，通过VerifyNow P2 Y12（Accumetrics Inc.，圣地亚哥，加州），CYP 2C 19 *2，*17，CYP 3A 5 *3和ABCB 1多态性在300例患者中进行了评价。死亡，中风，心肌梗死和眼睑被评估了1 year.Results氯吡格雷PR随时间变化显着，在基线高于1和6个月后。从基线到1个月，300例患者中有83例的缓解状态发生变化。这主要是由于基线差应答者变为完全应答者（75/83）。基因型证明了这一趋势的大约18%。随着时间的推移，CYP 2C 19 *2和 *17对PR的影响是一致的，而ABCB 1在基线时的影响似乎更大。氯吡格雷治疗1个月后PR独立预测缺血和出血事件最佳。我们发现了一个治疗窗口（86至238 P2 Y（12）反应单位），缺血和出血并发症的发生率较低。结合基因型（ABCB 1和CYP 2C 19 *2），基线PR和肌酐清除率来预测1个月的不良反应和1年的不良预后。结论在稳定状态下接受经皮冠状动脉介入治疗的氯吡格雷患者中，PR从基线下降到1个月。基因型对这一趋势的影响约为18%。氯吡格雷治疗后1个月的PR是不良结局的最强预测因子，这可以通过结合基因型与基线表型和临床变量进行预测。（J Am科尔心脏病学杂志2011; 57：2474-83）（C）美国心脏病学会基金会2011年
Objectives This study sought to investigate the evolving pattern over time of on-clopidogrel platelet reactivity (PR) and its relationship with genotype and clinical outcomes after percutaneous coronary intervention.Background Whether on-clopidogrel PR and role of genotype differ over time is unknown.Methods On-clopidogrel PR before percutaneous coronary intervention, and 1 and 6 months thereafter via VerifyNow P2Y12 (Accumetrics Inc., San Diego, California), CYP2C19*2, *17, CYP3A5*3, and ABCB1 polymorphisms were evaluated in 300 patients. Death, stroke, myocardial infarction, and bleedings were assessed up to 1 year.Results On-clopidogrel PR varied significantly over time, being higher at baseline than at 1 and 6 months after. From baseline to 1 month, 83 of 300 patients varied their response status. This was mainly due to baseline poor responders becoming full responders (75 of 83). Genotype justifies roughly 18% of this trend. CYP2C19*2 and *17 influence on PR was consistent over time, whereas that of ABCB1 appeared of greater impact at baseline. On-clopidogrel PR at 1 month independently best predicts ischemic and bleeding events. We found a therapeutic window (86 to 238 P2Y(12) reactivity units) with a lower incidence of both ischemic and bleeding complications. A risk score was created by combining genotype (ABCB1 and CYP2C19*2), baseline PR, and creatinine clearance to predict 1-month poor responsiveness and 1-year poor prognosis.Conclusions In patients at steady state for clopidogrel undergoing percutaneous coronary intervention, PR decreases from baseline to 1 month. Genotype influences approximate to 18% of this trend. On-clopidogrel PR at 1 month is the strongest predictor of adverse outcomes, and this can be predicted by combining genotype to baseline phenotype and clinical variables. (J Am Coll Cardiol 2011; 57: 2474-83) (C) 2011 by the American College of Cardiology Foundation