Please use this identifier to cite or link to this item: https://ahro.austin.org.au/austinjspui/handle/1/28063
Title: Cerebral Microbleeds and Treatment Effect of Intravenous Thrombolysis in Acute Stroke: An Analysis of the WAKE-UP Randomized Clinical Trial.
Austin Authors: Schlemm, Ludwig;Braemswig, Tim Bastian;Boutitie, Florent;Vynckier, Jan;Jensen, Märit;Galinovic, Ivana;Simonsen, Claus Z;Cheng, Bastian;Cho, Tae-Hee;Fiehler, Jens;Puig, Josep;Thijs, Vincent N ;Fiebach, Jochen;Muir, Keith;Nighoghossian, Norbert;Ebinger, Martin;Pedraza, Salvador;Thomalla, Götz;Gerloff, Christian;Endres, Matthias;Lemmens, Robin;Nolte, Christian H
Affiliation: German Center for Neurodegenerative Diseases (DZNE), Partner Site Berlin, Berlin, Germany
The Florey Institute of Neuroscience and Mental Health
Klinik und Hochschulambulanz für Neurologie, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health (BIH), Berlin, Germany
Center for Stroke Research Berlin (CSB), Charité - Universitätsmedizin, Berlin, Germany
Berlin Institute of Health (BIH), Berlin, Germany
Hospices Civils de Lyon, Service de Biostatistique, Lyon, France
Université Lyon 1 and Centre National de la Recherche Scientifique, UMR 5558, Laboratoire de Biométrie et Biologie Evolutive, Equipe Biostatistique-Santé, Villeurbanne, France
Department of Neurology, Medical Park Berlin Humboldtmühle, Berlin, Germany
Department of Neurology, University Hospitals Leuven, Leuven, Belgium
Department of Neurosciences, Experimental Neurology, KU Leuven-University of Leuven, Leuven, Belgium
VIB-KU Leuven Center for Brain and Disease Research, Laboratory of Neurobiology, Leuven, Belgium
Klinik und Hochschulambulanz für Neurologie, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health (BIH), Berlin, Germany. Center for Stroke Research Berlin (CSB), Charité - Universitätsmedizin, Berlin, Germany
Berlin Institute of Health (BIH), Berlin, Germany
German Center for Cardiovascular Research (DZHK), Partner Site Berlin, Berlin, Germany
Department of Neurology, University Hospital Bern, Bern, Switzerland
Klinik und Poliklinik für Neurologie, Kopf- und Neurozentrum, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany
Center for Stroke Research Berlin (CSB), Charité - Universitätsmedizin, Berlin, Germany
Department of Neurology, Aarhus University Hospital, Aarhus, Denmark
Klinik und Poliklinik für Neurologie, Kopf- und Neurozentrum, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany
Department of Stroke Medicine, Université Claude Bernard Lyon 1, and Hospices Civils de Lyon, Lyon, France
Department of Diagnostic and Interventional Neuroradiology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
Department of Radiology, Hospital Universitari Doctor Josep Trueta, Institut d'Investigació Biomèdica de Girona, Girona, Spain
Center for Stroke Research Berlin (CSB), Charité - Universitätsmedizin, Berlin, Germany
Institute of Neuroscience and, University of Glasgow, Glasgow, United Kingdom
Department of Stroke Medicine, Université Claude Bernard Lyon 1, and Hospices Civils de Lyon, Lyon, France
Department of Radiology, Hospital Universitari Doctor Josep Trueta, Institut d'Investigació Biomèdica de Girona, Girona, Spain
Klinik und Poliklinik für Neurologie, Kopf- und Neurozentrum, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany
Issue Date: 18-Jan-2022
Date: 2021
Publication information: Neurology 2022; 98(3): e302-e314
Abstract: Cerebral microbleeds (CMBs) are common in acute ischemic stroke patients and are associated with increased risk of intracerebral hemorrhage (ICH) after intravenous thrombolysis. Whether CMBs modify the treatment effect of thrombolysis is unknown. We performed a pre-specified analysis of the prospective randomized controlled multicenter WAKE-UP trial including patients with acute ischemic stroke with unknown time of symptom onset and DWI-FLAIR mismatch on MRI receiving alteplase or placebo. Patients were screened and enrolled between September 2012 and June 2017 (with final follow-up in September 2017). Patients were randomized to treatment with intravenous thrombolysis with alteplase at 0.9 mg / kg body weight or placebo. CMB status (presence, number, and distribution) was assessed after study completion by three raters blinded to clinical information following a standardized protocol. Outcome measures were excellent functional outcome at 90 days, defined by modified Rankin Scale score (mRS)≤1, and symptomatic intracerebral hemorrhage (ICH) according to NINDS trial criteria 22 to 36 hours after treatment. Of 503 patients enrolled in the WAKE-UP trial, 459 (91.3%; 288 [63%] men) were available for analysis; 98 (21.4%) had at least 1 CMB on baseline imaging; 45 (9.8%) had exactly 1 CMB, 37 (8.1%) had 2-4 CMBs, and 16 (3.5%) had ≥5 CMBs. Presence of CMBs was associated with a non-significant increased risk of symptomatic ICH (11.2% versus 4.2%; adjusted odds ratio 2.32 [95% CI 0.99-5.43]; P=.052), but had no effect on functional outcome at 90 days (mRS≤1: 45.8% versus 50.7%; adj. OR 0.99 [0.59-1.64]; P=.955). Patients receiving alteplase had better functional outcome (mRS≤1: 54.6% versus 44.6%, adj. OR 1.61 [1.07-2.43], P=.022) without evidence of heterogeneity in relation to CMB presence (P value of the interactive term .546). Results were similar for subpopulations with strictly lobar (presumed cerebral amyloid angiopathy-related) or non-strictly-lobar CMB distribution. In the randomized-controlled WAKE-UP trial, we saw no evidence of reduced treatment effect of alteplase in acute ischemic stroke patients with one or more CMBs. Additional studies are needed to determine the treatment effect of alteplase and its benefit-harm-ratio in patients with a larger number of CMBs. ClinicalTrials.gov number, NCT01525290 (https://clinicaltrials.gov/ct2/show/NCT01525290); EudraCT number, 2011-005906-32 (https://www.clinicaltrialsregister.eu/ctr-search/trial/2011-005906-32/GB). This study provides Class II evidence that for patients with acute ischemic stroke with unknown time of onset and DWI-FLAIR mismatch who received IV alteplase, CMBs are not significantly associated with functional outcome at 90 days.
URI: https://ahro.austin.org.au/austinjspui/handle/1/28063
DOI: 10.1212/WNL.0000000000013055
ORCID: 0000-0003-4165-2366
0000-0001-6112-2800
0000-0001-5338-961X
0000-0001-7793-0941
0000-0001-8533-7478
0000-0002-6614-8417
0000-0002-7936-6958
0000-0001-9535-022X
0000-0002-4948-5956
0000-0001-5577-1775
Journal: Neurology
PubMed URL: 34782419
Type: Journal Article
Appears in Collections:Journal articles

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