Cardiovascular Institute, Azienda Ospedaliero-Universitaria Sant'Anna, LTTA Center, Ferrara, Italy.
J Am Coll Cardiol. 2011 Jun 21;57(25):2474-83. doi: 10.1016/j.jacc.2010.12.047.
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.
Whether on-clopidogrel PR and role of genotype differ over time is unknown.
On-clopidogrel PR before percutaneous coronary intervention, and 1 and 6 months thereafter via VerifyNow P2Y12 (Accumetrics Inc., San Diego, California), CYP2C19*2, 17, CYP3A53, and ABCB1 polymorphisms were evaluated in 300 patients. Death, stroke, myocardial infarction, and bleedings were assessed up to 1 year.
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 P2Y₁₂ reactivity units) with a lower incidence of both ischemic and bleeding complications. A risk score was created by combining genotype (ABCB1 and CYP2C192), baseline PR, and creatinine clearance to predict 1-month poor responsiveness and 1-year poor prognosis.
In patients at steady state for clopidogrel undergoing percutaneous coronary intervention, PR decreases from baseline to 1 month. Genotype influences ≈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.
本研究旨在探讨经皮冠状动脉介入治疗（PCI）后氯吡格雷抵抗（PR）的演变模式及其与基因分型和临床结局的关系。
氯吡格雷抵抗的时间变化和基因分型的作用尚不清楚。
在 300 例患者中，通过 VerifyNow P2Y12（Accumetrics Inc.，加利福尼亚圣地亚哥）评估 PCI 前、PCI 后 1 个月和 6 个月的氯吡格雷抵抗，并评估 CYP2C19*2、17、CYP3A53 和 ABCB1 多态性。评估 1 年内的死亡、卒中和心肌梗死以及出血情况。
氯吡格雷抵抗在时间上变化显著，基线时高于 1 个月和 6 个月时。从基线到 1 个月，300 例患者中有 83 例患者的反应状态发生变化。这主要是由于基线时反应不良的患者变为完全反应者（75/83）。基因分型大致解释了这一趋势的 18%。CYP2C192 和17 对 PR 的影响在时间上是一致的，而 ABCB1 的影响在基线时更大。1 个月时的氯吡格雷抵抗独立预测缺血和出血事件。我们发现了一个治疗窗口（86 至 238 P2Y₁₂反应单位），其缺血和出血并发症的发生率较低。通过结合基因型（ABCB1 和 CYP2C19*2）、基线 PR 和肌酐清除率，创建了一个风险评分来预测 1 个月时的不良反应和 1 年时的不良预后。
在稳定接受氯吡格雷 PCI 的患者中，PR 从基线到 1 个月逐渐降低。基因分型约影响这一趋势的 18%。1 个月时的氯吡格雷抵抗是不良结局的最强预测因子，通过将基因型与基线表型和临床变量相结合，可以预测这种情况。
