双联抗血小板治疗与小卒中或短暂性脑缺血发作的病因：CHANCE-2 试验的预先设定分析。
Dual Antiplatelet Therapies and Causes in Minor Stroke or Transient Ischemic Attack: A Prespecified Analysis in the CHANCE-2 Trial.
机构信息
China National Clinical Research Center for Neurological Diseases, Beijing (X.X., J.J., X.M., Z.L., X.Z., L.L., Yilong Wang, Q.X., A.W., Y.J., H.L., Yongjun Wang).
Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, China (X.X., J.J., X.M., Z.L., X.Z., L.L., Yilong Wang, Q.X., A.W., Y.J., H.L., Yongjun Wang).
出版信息
Stroke. 2023 Sep;54(9):2241-2250. doi: 10.1161/STROKEAHA.122.042233. Epub 2023 Aug 7.
BACKGROUND
It is unclear whether patients with different stroke/transient ischemic attack etiologies benefit differently from gene-directed dual antiplatelet therapy. This study explored the efficacy and safety of ticagrelor-aspirin versus clopidogrel-aspirin in transient ischemic attack or minor stroke with different causes in the CHANCE-2 trial (Clopidogrel in High-Risk Patients With Acute Nondisabling Cerebrovascular Events-II).
METHODS
This was a prespecified analysis of the CHANCE-2 trial, which enrolled 6412 patients with minor stroke or transient ischemic attack who carried loss-of-function alleles. Patients with centralized evaluation of TOAST (Trial of ORG 10172 in Acute Stroke Treatment) classification of large-artery atherosclerosis, small-vessel occlusion, and stroke of undetermined cause were included. The primary efficacy outcome was new stroke, and the primary safety outcome was severe or moderate bleeding, both within 90 days. Cox proportional hazards models were used to assess the interaction of TOAST classification with the effects of dual antiplatelet therapy with ticagrelor-aspirin versus clopidogrel-aspirin.
RESULTS
A total of 6336 patients were included in this study. In patients administered ticagrelor-aspirin and clopidogrel-aspirin, respectively, stroke recurred in 85 (9.8%) and 88 (10.7%) patients with large-artery atherosclerosis (hazard ratio, 0.86 [95% CI, 0.63-1.18]; =0.34); 32 (3.6%) and 61 (7.0%) patients with small-vessel occlusion (hazard ratio, 0.51 [95% CI, 0.33-0.79]; =0.002); and 68 (4.8%) and 87 (5.9%) patients with stroke of undetermined cause (hazard ratio, 0.80 [95% CI, 0.58-1.10]; =0.17), with =0.08 for the treatment×cause subtype interaction effect. There were no significant differences in severe or moderate bleeding events in patients with different cause and different treatment.
CONCLUSIONS
In this prespecified analysis of the CHANCE-2 trial, the efficacy and safety of ticagrelor-aspirin versus clopidogrel-aspirin in preventing new stroke were consistent in patients with different causes. The influence of stroke cause on benefit of gene-guided antiplatelet therapy should be explored by further trials.
REGISTRATION
URL: https://www.
CLINICALTRIALS
gov; Unique identifier: NCT04078737.
背景
目前尚不清楚不同类型的卒中和短暂性脑缺血发作患者是否能从基因指导的双联抗血小板治疗中获得不同的获益。本研究旨在探讨替格瑞洛-阿司匹林与氯吡格雷-阿司匹林在 CHANCE-2 试验（氯吡格雷在伴有急性非致残性脑血管事件的高危患者-2）中不同病因的短暂性脑缺血发作或小卒中患者中的疗效和安全性。
方法
这是 CHANCE-2 试验的一项预设分析，共纳入 6412 例携带功能丧失等位基因的小卒中和短暂性脑缺血发作患者。纳入接受 TOAST（急性卒中治疗中 ORG 10172 试验）分类为大动脉粥样硬化、小血管闭塞和病因不明的卒中患者。主要疗效终点为 90 天内新发卒中，主要安全性终点为严重或中度出血。采用 Cox 比例风险模型评估 TOAST 分类与替格瑞洛-阿司匹林与氯吡格雷-阿司匹林双联抗血小板治疗效果之间的交互作用。
结果
共纳入 6336 例患者。分别接受替格瑞洛-阿司匹林和氯吡格雷-阿司匹林治疗的患者中，大动脉粥样硬化亚组分别有 85（9.8%）和 88（10.7%）例患者发生卒中（风险比，0.86 [95%CI，0.63-1.18]；=0.34），小血管闭塞亚组分别有 32（3.6%）和 61（7.0%）例患者发生卒中（风险比，0.51 [95%CI，0.33-0.79]；=0.002），病因不明亚组分别有 68（4.8%）和 87（5.9%）例患者发生卒中（风险比，0.80 [95%CI，0.58-1.10]；=0.17），治疗×病因亚组交互作用效应的=0.08。不同病因和不同治疗组之间严重或中度出血事件无显著差异。
结论
在 CHANCE-2 试验的这项预设分析中，替格瑞洛-阿司匹林与氯吡格雷-阿司匹林预防新发卒中的疗效和安全性在不同病因患者中一致。应通过进一步的试验来探讨卒中病因对基因指导的抗血小板治疗获益的影响。
注册
临床试验
gov；独特标识符：NCT04078737。
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