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Title: Intravenous Thrombolysis in Patients With White Matter Hyperintensities in the WAKE-UP Trial.
Austin Authors: Frey, Benedikt M;Shenas, Farhad;Boutitie, Florent;Cheng, Bastian;Cho, Tae-Hee;Ebinger, Martin;Endres, Matthias;Fiebach, Jochen B;Fiehler, Jens;Galinovic, Ivana;Barow, Ewgenia;Königsberg, Alina;Schlemm, Eckhard;Pedraza, Salvador;Lemmens, Robin;Thijs, Vincent N ;Muir, Keith W;Nighoghossian, Norbert;Simonsen, Claus Z;Gerloff, Christian;Thomalla, Götz
Affiliation: Klinik und Poliklinik für Neurologie, Kopf- und Neurozentrum, University Medical Center Hamburg-Eppendorf, Germany
Université Lyon 1, FranceCNRS, UMR 5558, Laboratoire de Biométrie et Biologie Evolutive, Equipe Biostatistique-Santé, Villeurbanne, France
Hospices Civils de Lyon, France
Department of Stroke Medicine, Université Claude Bernard Lyon 1, CREATIS CNRS UMR 5220-INSERM U1206, INSA-Lyon
Centrum für Schlaganfallforschung Berlin, Charité - Universitätsmedizin Berlin, Berlin, Germany
Klinik und Hochschulambulanz für Neurologie, Charité-Universitätsmedizin Berlin, Germany
Centrum für Schlaganfallforschung Berlin, Charité - Universitätsmedizin Berlin, Berlin, Germany
Department of Diagnostic and Interventional Neuroradiology, University Medical Center Hamburg-Eppendorf, Germany (J.F.).
Centrum für Schlaganfallforschung Berlin, Charité - Universitätsmedizin Berlin, Berlin, Germany (M. Ebinger, M. Endres, J.B.F., I.G.).
Neurologie der Rehaklinik Medical Park Humboldtmühle, Berlin, Germany
Leuven - University of Leuven, Department of Neurosciences, Experimental Neurology, Belgium
Center for Brain & Disease Research, Laboratory of Neurobiology, Campus Gasthuisberg, Belgium
Department of Radiology, Institut de Diagnostic per la Image, Hospital Dr Josep Trueta, Institut d'Investigació Biomèdica de Girona (IDIBGI), Parc Hospitalari Martí i Julià de Salt, Girona, Spain
Department of Neurology, University Hospitals Leuven, Belgium
The Florey Institute of Neuroscience and Mental Health
Institute of Neuroscience & Psychology, University of Glasgow, University Avenue, Glasgow, United Kingdom
Department of Neurology, Aarhus University Hospital, Denmark
Issue Date: Jul-2023
Date: 2023
Publication information: Stroke 2023-07; 54(7)
Abstract: 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. 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. 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 (P=0.443) or any hemorrhagic transformation (P=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]). 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. URL: https://www. gov; Unique identifier: NCT01525290.
DOI: 10.1161/STROKEAHA.122.040247
ORCID: 0000-0002-5302-0801
Journal: Stroke
PubMed URL: 37226772
ISSN: 1524-4628
Type: Journal Article
Subjects: alteplase
cerebral small vessel disease
ischemic stroke
thrombolytic therapy
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