Thrombolysis for Wake-Up Stroke Versus Non-Wake-Up Unwitnessed Stroke: EOS Individual Patient Data Meta-Analysis.

Autor:	Kamogawa N; Department of Cerebrovascular Medicine, National Cerebral and Cardiovascular Center, Suita, Japan (N.K., K.M., K.T., M.I., S.Y., M.K.)., Miwa K; Department of Cerebrovascular Medicine, National Cerebral and Cardiovascular Center, Suita, Japan (N.K., K.M., K.T., M.I., S.Y., M.K.)., Toyoda K; Department of Cerebrovascular Medicine, National Cerebral and Cardiovascular Center, Suita, Japan (N.K., K.M., K.T., M.I., S.Y., M.K.)., Jensen M; Klinik und Poliklinik für Neurologie, Kopf- und Neurozentrum, Universitätsklinikum Hamburg-Eppendorf, Germany (M.J., C.G., G.T.)., Inoue M; Department of Cerebrovascular Medicine, National Cerebral and Cardiovascular Center, Suita, Japan (N.K., K.M., K.T., M.I., S.Y., M.K.)., Yoshimura S; Department of Cerebrovascular Medicine, National Cerebral and Cardiovascular Center, Suita, Japan (N.K., K.M., K.T., M.I., S.Y., M.K.)., Fukuda-Doi M; Center for Advancing Clinical and Translational Sciences, National Cerebral, and Cardiovascular Center, Suita, Japan (M.F.-D.)., Kitazono T; Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan (T.K.)., Boutitie F; Hospices Civils de Lyon, Service de Biostatistique, France (F.B.).; Villeurbanne, France; Laboratoire de Biométrie et Biologie Evolutive, Equipe Biostatistique-Santé, Villeurbanne, France (F.B.)., Ma H; Department of Medicine, School of Clinical Sciences, Monash University, Melbourne, VIC, Australia (H.M.)., Ringleb P; Department of Neurology, University of Heidelberg, Germany (P.R., W.H.)., Wu O; Athinoula A Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Charlestown (O.W.)., Schwamm LH; Department of Neurology, Massachusetts General Hospital, Boston (L.H.S.)., Warach S; Dell Medical School, University of Texas at Austin (S.W.)., Hacke W; Department of Neurology, University of Heidelberg, Germany (P.R., W.H.)., Davis SM; Departments of Medicine and Neurology, Melbourne Brain Centre at the Royal Melbourne Hospital, the University of Melbourne, VIC, Australia (S.M.D., G.A.D.)., Donnan GA; Departments of Medicine and Neurology, Melbourne Brain Centre at the Royal Melbourne Hospital, the University of Melbourne, VIC, Australia (S.M.D., G.A.D.)., Gerloff C; Klinik und Poliklinik für Neurologie, Kopf- und Neurozentrum, Universitätsklinikum Hamburg-Eppendorf, Germany (M.J., C.G., G.T.)., Thomalla G; Klinik und Poliklinik für Neurologie, Kopf- und Neurozentrum, Universitätsklinikum Hamburg-Eppendorf, Germany (M.J., C.G., G.T.)., Koga M; Department of Cerebrovascular Medicine, National Cerebral and Cardiovascular Center, Suita, Japan (N.K., K.M., K.T., M.I., S.Y., M.K.).
Jazyk:	angličtina
Zdroj:	Stroke [Stroke] 2024 Apr; Vol. 55 (4), pp. 895-904. Date of Electronic Publication: 2024 Mar 08.
DOI:	10.1161/STROKEAHA.123.043358
Abstrakt:	Background: Stroke with unknown time of onset can be categorized into 2 groups; wake-up stroke (WUS) and unwitnessed stroke with an onset time unavailable for reasons other than wake-up (non-wake-up unwitnessed stroke, non-WUS). We aimed to assess potential differences in the efficacy and safety of intravenous thrombolysis (IVT) between these subgroups. Methods: Patients with an unknown-onset stroke were evaluated using individual patient-level data of 2 randomized controlled trials (WAKE-UP [Efficacy and Safety of MRI-Based Thrombolysis in Wake-Up Stroke], THAWS [Thrombolysis for Acute Wake-Up and Unclear-Onset Strokes With Alteplase at 0.6 mg/kg]) comparing IVT with placebo or standard treatment from the EOS (Evaluation of Unknown-Onset Stroke Thrombolysis trial) data set. A favorable outcome was prespecified as a modified Rankin Scale score of 0 to 1 at 90 days. Safety outcomes included symptomatic intracranial hemorrhage at 22 to 36 hours and 90-day mortality. The IVT effect was compared between the treatment groups in the WUS and non-WUS with multivariable logistic regression analysis. Results: Six hundred thirty-four patients from 2 trials were analyzed; 542 had WUS (191 women, 272 receiving alteplase), and 92 had non-WUS (42 women, 43 receiving alteplase). Overall, no significant interaction was noted between the mode of onset and treatment effect ( P value for interaction=0.796). In patients with WUS, the frequencies of favorable outcomes were 54.8% and 45.5% in the IVT and control groups, respectively (adjusted odds ratio, 1.47 [95% CI, 1.01-2.16]). Death occurred in 4.0% and 1.9%, respectively ( P =0.162), and symptomatic intracranial hemorrhage in 1.8% and 0.3%, respectively ( P =0.194). In patients with non-WUS, no significant difference was observed in favorable outcomes relative to the control (37.2% versus 29.2%; adjusted odds ratio, 1.76 [0.58-5.37]). One death and one symptomatic intracranial hemorrhage were reported in the IVT group, but none in the control. Conclusions: There was no difference in the effect of IVT between patients with WUS and non-WUS. IVT showed a significant benefit in patients with WUS, while there was insufficient statistical power to detect a substantial benefit in the non-WUS subgroup. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: CRD42020166903. Competing Interests: Disclosures Dr Ma has consulted for Independent Sector. Dr Ringleb has consulted for Boehringer Ingelheim and Daiichi Sankyo Company and reports personal fees from Bayer Healthcare and Bristol-Myers Squibb. Dr Wu reports grants from National Institutes of Health. Dr Schwamm serves as a scientific consultant regarding trial design and conduct to Genentech (late-window thrombolysis) and as a member of steering committee (TIMELESS [A Phase III, Prospective, Double-Blind, Randomized, Placebo-Controlled Trial of Thrombolysis in Imaging-Eligible, Late-Window Patients to Assess the Efficacy and Safety of Tenecteplase] NCT03785678); stroke systems of care consultant to the Massachusetts Dept of Public Health; member of a Data Safety Monitoring Boards (DSMB) for Penumbra (MIND NCT03342664) and for Diffusion Pharma PHAST-TSC (Double-Blind, Randomized, Placebo-Controlled, Phase 2 Study of Efficacy and Safety of Trans Sodium Crocetinate [TSC] Administered Onboard Emergency Vehicles for Treatment of Suspected Stroke; NCT03763929); and delivering continuing medical education lectures for Boehringer Ingelheim and Prime Education: stroke systems of care and improving time to thrombolysis. Dr Warach has consulted for Genentech. Dr Davis reports personal fees from Boehringer Ingelheim. Dr Donnan has consulted for Amgen. Dr Gerloff has consulted for Abbott Canada, Allergan, Amgen, Astra-Zeneca, Bayer Healthcare, and Boehringer Ingelheim and reports grants from Deutsche Forschungsgemeinschaft, Deutsches Zentrum für Luft- und Raumfahrt, European Union, Gemeinnützige Hertie-Stiftung, Merz Farmaceutica Comercial LTDA, and Schilling-Stiftung. Dr Thomalla has consulted for Acandis, Bayer, PORTOLA PHARMACEUTICALS, LLC, and Stryker and reports personal fees from Alexion Pharmaceuticals Inc, Amarin Pharma Inc, Boehringer Ingelheim, Bristol-Myers Squibb, and Daiichi Sankyo Europe GmbH. Dr Kitazono reports grant from Daiichi Sankyo Company LTD. Dr Toyoda has consulted for Otsuka Pharmaceutical and reports personal fees from Abbott Japan, Bayer, Bristol-Myers Squibb, Daiichi Sankyo, and Novartis. Dr Koga has consulted for Janssen Pharmaceuticals, reports personal fees from Daiichi Sankyo Company, Bayer, Bristol-Myers Squibb, Mitsubishi Tanabe Pharma Corporation and Pfizer, and reports grants from Daiichi Sankyo Company LTD, Nippon Boehringer Ingelheim Co Ltd. The other authors report no conflicts.
Databáze:	MEDLINE
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