Department of Neurology, National Cerebral and Cardiovascular Center.
Division of Stroke Care Unit, National Cerebral and Cardiovascular Center.
J Atheroscler Thromb. 2023 Jan 1;30(1):39-55. doi: 10.5551/jat.63369. Epub 2022 Mar 5.
We aimed to determine the association between acute platelet reactivity and clinical outcome in acute ischemic stroke (AIS) or transient ischemic attack (TIA) with large-artery atherosclerosis (LAA).
In this prospective, 16-multicenter study, we enrolled AIS/TIA patients with LAA receiving clopidogrel. We assessed the association of P2Y12 reaction units (PRU) 24 hours after initiation of antiplatelets with the CYP2C19 genotype and recurrent ischemic stroke within 90 days, and the difference between acute (≤ 7 days) and subacute (8-90 days) phases.
Among the 230 AIS/TIA patients enrolled, 225 with complete outcome data and 194 with genetic results were analyzed. A higher PRU was significantly associated with recurrent ischemic stroke within 90 days (frequency, 16%), and within 7 days (10%). Twenty-nine patients (15%) belonged to a CYP2C19 poor metabolizer group (CYP2C192/2, 2/3, or 3/3). Multivariable receiver-operating characteristic analysis showed a greater area-under-the-curve (AUC) in predicting recurrence within 7 days, compared to 8-90 days (AUC, 0.79 versus 0.64; p=0.07), with a cut-off PRU of 254. Multivariable analysis showed high PRU (≥ 254), which had a comparable predictive performance for recurrent ischemic stroke within 7 days (odds ratio, 6.82; 95% CI, 2.23-20.9; p＜0.001) to the CYP2C19 poor metabolizer genotype. The net reclassification improvement, calculated by adding high PRU (≥ 254) to a model including the CYP2C19 poor metabolizer genotype in the prediction of recurrence within 7 days, was 0.83 (p＜0.001).
Acute PRU evaluation possesses predictive value for recurrent ischemic stroke, especially within 7 days in AIS/TIA with LAA.
本研究旨在探讨急性血小板反应性与大动脉粥样硬化性急性缺血性卒中和短暂性脑缺血发作（TIA）患者临床预后的相关性。
本前瞻性、16 中心研究纳入了接受氯吡格雷治疗的大动脉粥样硬化性急性缺血性卒中和 TIA 患者。我们评估了抗血小板治疗 24 小时后的 P2Y12 反应单位（PRU）与 CYP2C19 基因型及 90 天内复发性缺血性卒中之间的相关性，以及急性（≤7 天）和亚急性（8-90 天）两个阶段之间的差异。
在纳入的 230 例急性缺血性卒中和 TIA 患者中，对 225 例有完整结局数据和 194 例有基因检测结果的患者进行了分析。较高的 PRU 与 90 天内（频率为 16%）和 7 天内（频率为 10%）的复发性缺血性卒中显著相关。29 例（15%）患者属于 CYP2C19 弱代谢组（CYP2C192/2、2/3 或 3/3）。多变量受试者工作特征分析显示，预测 7 天内复发的曲线下面积（AUC）大于预测 8-90 天内复发的 AUC（AUC 分别为 0.79 和 0.64；p=0.07），预测 7 天内复发的最佳 PRU 截断值为 254。多变量分析显示，高 PRU（≥254）与 CYP2C19 弱代谢基因型对 7 天内复发性缺血性卒中的预测具有相当的性能（比值比，6.82；95%可信区间，2.23-20.9；p＜0.001）。通过在预测 7 天内复发的模型中加入高 PRU（≥254），对预测模型进行校正后，净重新分类改善为 0.83（p＜0.001）。
急性 PRU 评估对大动脉粥样硬化性急性缺血性卒中和 TIA 患者复发性缺血性卒中具有预测价值，特别是在 7 天内。
