WAKE-UP 试验中存在脑白质高信号的患者的静脉溶栓治疗。
Intravenous Thrombolysis in Patients With White Matter Hyperintensities in the WAKE-UP Trial.
机构信息
Klinik und Poliklinik für Neurologie, Kopf- und Neurozentrum, University Medical Center Hamburg-Eppendorf, Germany (B.M.F., F.S., B.C., E.B., A.K., E.S., C.G., G.T.).
Hospices Civils de Lyon, Service de Biostatistique, F-69003 Lyon, France; Université Lyon 1, France; CNRS, UMR 5558, Laboratoire de Biométrie et Biologie Evolutive, Equipe Biostatistique-Santé, Villeurbanne, France (F.B.).
出版信息
Stroke. 2023 Jul;54(7):1718-1725. doi: 10.1161/STROKEAHA.122.040247. Epub 2023 May 25.
BACKGROUND
White matter hyperintensities of presumed vascular origin (WMH) are the most prominent imaging feature of cerebral small vessel disease (cSVD). Previous studies suggest a link between cSVD burden and intracerebral hemorrhage and worse functional outcome after thrombolysis in acute ischemic stroke. We aimed to determine the impact of WMH burden on efficacy and safety of thrombolysis in the MRI-based randomized controlled WAKE-UP trial of intravenous alteplase in unknown onset stroke.
METHODS
The design of this post hoc study was an observational cohort design of a secondary analysis of a randomized trial. WMH volume was quantified on baseline fluid-attenuated inversion recovery images of patients randomized to either alteplase or placebo in the WAKE-UP trial. Excellent outcome was defined as score of 0-1 on the modified Rankin Scale after 90 days. Hemorrhagic transformation was assessed on follow-up imaging 24-36 hours after randomization. Treatment effect and safety were analyzed by fitting multivariable logistic regression models.
RESULTS
Quality of scans was sufficient in 441 of 503 randomized patients to delineate WMH. Median age was 68 years, 151 patients were female, and 222 patients were assigned to receive alteplase. Median WMH volume was 11.4 mL. Independent from treatment, WMH burden was statistically significantly associated with worse functional outcome (odds ratio, 0.72 [95% CI, 0.57-0.92]), but not with higher chances of any hemorrhagic transformation (odds ratio, 0.78 [95% CI, 0.60-1.01]). There was no interaction of WMH burden and treatment group for the likelihood of excellent outcome (=0.443) or any hemorrhagic transformation (=0.151). In a subgroup of 166 patients with severe WMH, intravenous thrombolysis was associated with higher odds of excellent outcome (odds ratio, 2.40 [95% CI, 1.19-4.84]) with no significant increase in the rate of hemorrhagic transformation (odds ratio, 1.96 [95% CI, 0.80-4.81]).
CONCLUSIONS
Although WMH burden is associated with worse functional outcome, there is no association with treatment effect or safety of intravenous thrombolysis in patients with ischemic stroke of unknown onset.
REGISTRATION
URL: https://www.
CLINICALTRIALS
gov; Unique identifier: NCT01525290.
背景
由血管原因引起的脑白质高信号（WMH）是脑小血管病（CSVD）最显著的影像学特征。先前的研究表明，CSVD 负担与脑出血之间存在关联，并且在急性缺血性卒中接受溶栓治疗后功能结局更差。我们旨在确定 WMH 负担对 WAKE-UP 试验中静脉注射阿替普酶治疗不明原因卒中的 MRI 随机对照研究的疗效和安全性的影响。
方法
本研究是一项随机试验的二次分析的观察性队列设计。在 WAKE-UP 试验中，将基线液体衰减反转恢复图像上随机分配至阿替普酶或安慰剂的患者的 WMH 体积进行量化。90 天后改良 Rankin 量表评分为 0-1 定义为良好结局。在随机分组后 24-36 小时进行随访成像以评估出血转化。通过拟合多变量逻辑回归模型来分析治疗效果和安全性。
结果
在 503 名随机患者中，有 441 名患者的扫描质量足以描绘 WMH。中位年龄为 68 岁，151 名患者为女性，222 名患者被分配接受阿替普酶治疗。中位 WMH 体积为 11.4ml。与治疗无关，WMH 负担与功能结局更差呈统计学显著相关（比值比，0.72 [95%CI，0.57-0.92]），但与任何出血转化的可能性无关（比值比，0.78 [95%CI，0.60-1.01]）。WMH 负担和治疗组对良好结局的可能性（=0.443）或任何出血转化的可能性（=0.151）之间没有交互作用。在 166 名 WMH 严重的患者亚组中，静脉溶栓与良好结局的可能性更高相关（比值比，2.40 [95%CI，1.19-4.84]），而出血转化的发生率无显著增加（比值比，1.96 [95%CI，0.80-4.81]）。
结论
尽管 WMH 负担与功能结局更差相关，但在不明原因缺血性卒中患者中，静脉溶栓的治疗效果和安全性与 WMH 负担无关。
登记
网址：https://www.
临床试验
gov；唯一标识符：NCT01525290。
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