阿司匹林对小卒中或短暂性脑缺血发作患者血小板功能和临床结局的反应性。

Aspirin platelet reactivity on platelet function and clinical outcome in minor stroke or transient ischemic attack.

机构信息

Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, No 119 South 4th Ring West Road, Fengtai District, Beijing 100070, China; China National Clinical Research Center for Neurological Diseases, Beijing, China; Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing, China; Beijing Key Laboratory of Translational Medicine for Cerebrovascular Disease, Beijing, China; Department of Neurology, Beijing Long Fu Hospital, Beijing, China.

出版信息

J Stroke Cerebrovasc Dis. 2022 Sep;31(9):106683. doi: 10.1016/j.jstrokecerebrovasdis.2022.106683. Epub 2022 Jul 30.

DOI:10.1016/j.jstrokecerebrovasdis.2022.106683

PMID:35914511

Abstract

OBJECTIVE

Whether aspirin platelet reactivity affects platelet function and clinical outcomes with different antiplatelet therapies in patients with mild stroke or transient ischemic attack (TIA) remains unclear. We conducted a subgroup analysis of the PRINCE trial.

MATERIALS AND METHODS

Patients with mild stroke or TIA were randomized into aspirin+ticagrelor, or aspirin+clopidogrel groups; aspirin reaction units (ARU) were measured at the baseline and after 7 ± 2 days to assess response to treatment. High on-treatment platelet reactivity (HPR) was defined as ≥550 ARU (poor response to aspirin). The platelet functions of ticagrelor and clopidogrel were measured using the VerifyNow P2Y assay for P2Y reaction units (PRU); HPR to P2Y was defined as >208 PRU (poor response to P2Y). Clinical outcomes included stroke and clinical vascular and bleeding events after 90 days.

RESULTS

Among 628 enrolled patients, 69 (11%) were poor aspirin responders. After 7 ± 2 days, the proportion of poor P2Y responders for ticagrelor versus clopidogrel significantly reduced in poor (2.6% versus 27.4%) and good (14.3% versus 29.4%) aspirin responders. There were significant interactions between treatment groups, and between treatment groups and aspirin platelet reactivity for poor P2Y responders (P = 0.01). After 90 ± 7 days, there were no significant interactions between treatment groups and aspirin platelet reactivity for new stroke risk (good aspirin responders: 5.5% versus 8.8%, hazard ratio [HR]: 0.61; 95% confidence interval [CI], 0.32 to 1.16; P = 0.13; poor aspirin responders: 8.6% versus 8.8%, HR: 0.97, 95% CI: 0.20-4.81; P = 0.97; P for interaction = 0.60). Major bleeding was less frequent in poor than good aspirin responders (ticagrelor/aspirin: 0.4%/0%; clopidogrel/aspirin: 1.4%/0%).

CONCLUSIONS

In patients with minor stroke or TIA, clopidogrel, and particularly ticagrelor, decreased platelet function in poor versus good aspirin responders. The poor platelet reactivity of aspirin could not sufficiently reduce the risk of recurrent stroke with ticagrelor or clopidogrel; however, HPR (poor aspirin response) may have a protective effect on clinically relevant major bleeding.

摘要

目的

在轻度卒中和短暂性脑缺血发作（TIA）患者中，阿司匹林的血小板反应性是否会影响不同抗血小板治疗的血小板功能和临床结局尚不清楚。我们对 PRINCE 试验进行了亚组分析。

材料和方法

将轻度卒中和 TIA 患者随机分为阿司匹林+替格瑞洛或阿司匹林+氯吡格雷组；在基线和 7±2 天时测量阿司匹林反应单位（ARU），以评估治疗反应。高治疗血小板反应性（HPR）定义为≥550 ARU（阿司匹林反应差）。使用 VerifyNow P2Y 测定法测量替格瑞洛和氯吡格雷的血小板功能，以 P2Y 反应单位（PRU）表示；P2Y 的 HPR 定义为>208 PRU（P2Y 反应差）。临床结局包括 90 天后的卒中以及临床血管和出血事件。

结果

在 628 名入组患者中，有 69 名（11%）是阿司匹林低反应者。在 7±2 天后，在阿司匹林低反应者中，替格瑞洛与氯吡格雷相比，P2Y 低反应者的比例显著降低（分别为 2.6%和 27.4%）和阿司匹林高反应者（分别为 14.3%和 29.4%）。治疗组之间以及治疗组与阿司匹林血小板反应性之间存在显著的交互作用，对 P2Y 低反应者（P=0.01）。在 90±7 天后，治疗组之间与阿司匹林血小板反应性之间对新发卒中风险没有显著的交互作用（阿司匹林高反应者：5.5%对 8.8%，风险比[HR]：0.61；95%置信区间[CI]：0.32 至 1.16；P=0.13；阿司匹林低反应者：8.6%对 8.8%，HR：0.97，95% CI：0.20-4.81；P=0.97；交互作用 P 值=0.60）。阿司匹林低反应者的大出血发生率低于阿司匹林高反应者（替格瑞洛/阿司匹林：0.4%/0%；氯吡格雷/阿司匹林：1.4%/0%）。