不明来源栓塞性脑卒中患者的双联抗血小板治疗：CHANCE-2 试验的亚组分析。
Dual Antiplatelet Therapy After Embolic Stroke of Undetermined Source: A Subgroup Analysis of 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., Yilong Wang, Q.X., A.W., Y.J., H.L., Yongjun Wang).
Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China (X.X., J.J., X.M., Z.L., X.Z., Yilong Wang, Q.X., A.W., Y.J., H.L., Yongjun Wang).
出版信息
Stroke. 2024 Jul;55(7):1739-1747. doi: 10.1161/STROKEAHA.124.046834. Epub 2024 Jun 11.
BACKGROUND
The atherosclerotic sources of embolism are a significant contributor to embolic stroke of undetermined source (ESUS). However, there is limited evidence for the efficacy of intensive dual antiplatelet therapy for ESUS. We conducted an investigation to determine whether gene-directed dual antiplatelet therapy could reduce the risk of recurrent stroke in patients with ESUS.
METHODS
CHANCE-2 (Clopidogrel in High-Risk Patients with Acute Nondisabling Cerebrovascular Events-II) was an investigator-initiated, multicenter, randomized, double-blind, placebo-controlled trial that objectively compared ticagrelor plus aspirin and clopidogrel plus aspirin in patients with minor stroke or transient ischemic attack who carried loss-of-function alleles in China. All study participants were classified into ESUS and non-ESUS groups for the prespecified exploratory analysis. Cox proportional hazards models were used to assess the interaction of the state of ESUS with the effects of dual antiplatelet therapy with ticagrelor-aspirin versus clopidogrel-aspirin, adjusting for sociodemographic and clinical factors.
RESULTS
The subgroup analysis comprised 5796 participants (90.4% of the total 6412 participants) in the CHANCE-2 trial, with a median age of 64.9 years (range, 57.0-71.4 years), of whom 1964 (33.9%) were female. These participants underwent diffusion-weighted imaging as part of the study protocol. After systematic evaluation, 15.2% of patients (881/5796) were deemed to have ESUS. The incidence of stroke recurrence in patients with ESUS was found to be 5.6% in the ticagrelor-aspirin group and 9.2% in the clopidogrel-aspirin group (hazard ratio, 0.57 [95% CI, 0.33-0.99]; =0.04). In patients without ESUS, the respective incidence rates were 5.6% and 7.5% (hazard ratio, 0.72 [95% CI, 0.58-0.90]; <0.01). The value was 0.56 for the treatment × ESUS status interaction effect.
CONCLUSIONS
In this prespecified exploratory analysis, ticagrelor with aspirin was superior to clopidogrel with aspirin for preventing stroke at 90 days in patients with acute ischemic stroke or transient ischemic attack who carried loss-of-function alleles and were classified as ESUS.
REGISTRATION
URL: https://www.clinicaltrials.gov; Unique identifier: NCT04078737.
背景
动脉粥样硬化性栓塞是不明来源栓塞性卒中（ESUS）的重要病因。然而，强化双联抗血小板治疗对 ESUS 的疗效证据有限。我们开展了一项研究，旨在确定基因导向双联抗血小板治疗是否可以降低 ESUS 患者的复发性卒中风险。
方法
CHANCE-2（氯吡格雷在伴有急性非致残性脑血管事件的高危患者 II 期）是一项由研究者发起的、多中心、随机、双盲、安慰剂对照试验，客观比较了 Ticagrelor 联合阿司匹林与氯吡格雷联合阿司匹林在携带中国人群中功能丧失等位基因的小卒中和短暂性脑缺血发作患者中的疗效。所有研究参与者均按预先设定的探索性分析分为 ESUS 和非 ESUS 组。采用 Cox 比例风险模型评估 ESUS 状态与 Ticagrelor-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，调整社会人口统计学和临床因素。
结果
CHANCE-2 试验的亚组分析包括 5796 名参与者（总 6412 名参与者的 90.4%），中位年龄为 64.9 岁（范围为 57.0-71.4 岁），其中 1964 名（33.9%）为女性。这些参与者接受了扩散加权成像作为研究方案的一部分。经过系统评估，15.2%的患者（881/5796）被诊断为 ESUS。在 ESUS 患者中，Ticagrelor-阿司匹林组的卒中复发发生率为 5.6%，氯吡格雷-阿司匹林组为 9.2%（风险比，0.57[95%CI，0.33-0.99]；=0.04）。在无 ESUS 的患者中，相应的发生率分别为 5.6%和 7.5%（风险比，0.72[95%CI，0.58-0.90]；<0.01）。治疗×ESUS 状态交互作用的 P 值为 0.56。
结论
在这项预先设定的探索性分析中，与氯吡格雷联合阿司匹林相比，携带功能丧失等位基因且被归类为 ESUS 的急性缺血性卒中和短暂性脑缺血发作患者使用 Ticagrelor 联合阿司匹林可在 90 天时更有效地预防卒中。
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