Zhang Yanli, Wang Xuan, Gao Ying, Chen Weiqi, Johnston S Claiborne, Amarenco Pierre, Bath Philip M, Yan Hongyi, Wang Tingting, Yang Yingying, Zhou Qi, Wang Mengxing, Jing Jing, Wang Chunjuan, Wang Yongjun, Wang Yilong, Pan Yuesong
Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, China (Y.Z., X.W., Y.G., W.C., H.Y., T.W., Y.Y., Q.Z., M.W., J.J., C.W., Yongjun Wang, Yilong Wang, Y.P.).
China National Clinical Research Center for Neurological Diseases, Beijing (Y.Z., X.W., Y.G., W.C., H.Y., T.W., Y.Y., Q.Z., M.W., J.J., C.W., Yongjun Wang, Yilong Wang, Y.P.).
Stroke. 2025 Jan;56(1):46-55. doi: 10.1161/STROKEAHA.124.049246. Epub 2024 Dec 20.
Risk profile of recurrence may influence the effect of antiplatelet therapy. This study aimed to evaluate the efficacy and safety of clopidogrel-aspirin initiated within 72 hours after symptom onset for acute mild stroke or high-risk transient ischemic attack stratified by risk profile.
This is a secondary post hoc analysis of the INSPIRES (Intensive Statin and Antiplatelet Therapy for Acute High-risk Intracranial or Extracranial Atherosclerosis) randomized clinical trial that enrolled patients 35 to 80 years old with acute mild ischemic stroke or high-risk transient ischemic attack between 2018 and 2022. Patients were stratified into different groups based on the Essen Stroke Risk Score (ESRS) and modified ESRS. The primary efficacy outcome was any new stroke within 90 days. The primary safety outcome was moderate-to-severe bleeding within 90 days.
Among 6100 patients (3050 each in the clopidogrel-aspirin group and aspirin group), the median age was 65 years (interquartile range, 57-71 years), and 3915 (64.2%) were male. Clopidogrel-aspirin was associated with a reduced risk of new stroke in patients with an ESRS of <3 (hazard ratio [HR], 0.67 [95% CI, 0.52-0.86]), but not in those with an ESRS of ≥3 (HR, 0.92 [95% CI, 0.72-1.18]), compared with aspirin (=0.07). Similar results were found in patients stratified by modified ESRS (modified ESRS <6 in male and <5 in female: HR, 0.68 [95% CI, 0.55-0.83]; modified ESRS ≥6 in male and ≥5 in female: HR, 1.14 [95% CI, 0.82-1.59]; =0.01). The association between antiplatelet therapy and the moderate-to-severe bleeding did not differ across risk profile subgroups (ESRS of <3: HR, 1.35 [95% CI, 0.54-3.35]; ESRS of ≥3: HR, 3.21 [95% CI, 1.18-8.78]; =0.21; modified ESRS of <6 in male and <5 in female: HR, 1.96 [95% CI, 0.88-4.36]; modified ESRS of ≥6 in male and ≥5 in female: HR, 2.27 [95% CI, 0.70-7.39]; =0.85).
This post hoc analysis of the INSPIRES trial showed that patients with a low level of risk profile assessed by ESRS received greater benefit from clopidogrel-aspirin initiated within 72 hours after symptom onset than aspirin alone.
URL: https://www.clinicaltrials.gov; Unique identifier: NCT03635749.
复发风险特征可能会影响抗血小板治疗的效果。本研究旨在评估症状发作后72小时内开始使用氯吡格雷联合阿司匹林治疗对急性轻度卒中或高危短暂性脑缺血发作患者（根据风险特征分层）的疗效和安全性。
这是一项对INSPIRES（急性高危颅内或颅外动脉粥样硬化的强化他汀类药物和抗血小板治疗）随机临床试验的事后二次分析，该试验纳入了2018年至2022年间年龄在35至80岁的急性轻度缺血性卒中或高危短暂性脑缺血发作患者。根据埃森卒中风险评分（ESRS）和改良ESRS将患者分层为不同组。主要疗效结局为90天内发生的任何新发卒中。主要安全性结局为90天内发生的中至重度出血。
在6100例患者中（氯吡格雷联合阿司匹林组和阿司匹林组各3050例），中位年龄为65岁（四分位间距，57 - 71岁），男性3915例（64.2%）。与阿司匹林相比，ESRS <3的患者使用氯吡格雷联合阿司匹林可降低新发卒中风险（风险比[HR]，0.67 [95%置信区间，0.52 - 0.86]），但ESRS≥3的患者则不然（HR，0.92 [95%置信区间，0.72 - 1.18]）（P = 0.07）。在根据改良ESRS分层的患者中也发现了类似结果（男性改良ESRS <6且女性<5：HR，0.68 [95%置信区间，0.55 - 0.83]；男性改良ESRS≥6且女性≥5：HR，1.14 [95%置信区间，0.82 - 1.59]；P = 0.01）。抗血小板治疗与中至重度出血之间的关联在不同风险特征亚组中无差异（ESRS <3：HR，1.35 [95%置信区间，0.54 - 3.35]；ESRS≥3：HR，3.21 [95%置信区间，1.18 - 8.78]；P = 0.21；男性改良ESRS <6且女性<5：HR，1.96 [95%置信区间，0.88 - 4.36]；男性改良ESRS≥6且女性≥5：HR，2.27 [95%置信区间，0.70 - 7.39]；P = 0.85）。
INSPIRES试验的这项事后分析表明，对于症状发作后72小时内开始使用氯吡格雷联合阿司匹林治疗的患者，ESRS评估的低风险特征患者比单独使用阿司匹林获益更大。
