{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T16:19:28Z","timestamp":1792685968777,"version":"4.5.0"},"reference-count":34,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Stroke"],"published-print":{"date-parts":[[2024,4]]},"abstract":"<jats:sec>\n            <jats:title>BACKGROUND:<\/jats:title>\n            <jats:p>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\u2013wake-up unwitnessed stroke, non-WUS). We aimed to assess potential differences in the efficacy and safety of intravenous thrombolysis (IVT) between these subgroups.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>METHODS:<\/jats:title>\n            <jats:p>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.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>RESULTS:<\/jats:title>\n            <jats:p>\n              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 (\n              <jats:italic>P<\/jats:italic>\n              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\u20132.16]). Death occurred in 4.0% and 1.9%, respectively (\n              <jats:italic>P<\/jats:italic>\n              =0.162), and symptomatic intracranial hemorrhage in 1.8% and 0.3%, respectively (\n              <jats:italic>P<\/jats:italic>\n              =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\u20135.37]). One death and one symptomatic intracranial hemorrhage were reported in the IVT group, but none in the control.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>CONCLUSIONS:<\/jats:title>\n            <jats:p>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.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>REGISTRATION:<\/jats:title>\n            <jats:p>\n              URL:\n              <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/www.clinicaltrials.gov\">https:\/\/www.clinicaltrials.gov<\/jats:ext-link>\n              ; Unique identifier: CRD42020166903.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/strokeaha.123.043358","type":"journal-article","created":{"date-parts":[[2024,9,20]],"date-time":"2024-09-20T15:00:54Z","timestamp":1726844454000},"page":"895-904","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":11,"title":["Thrombolysis for Wake-Up Stroke Versus Non\u2013Wake-Up Unwitnessed Stroke: EOS Individual Patient Data Meta-Analysis"],"prefix":"10.1161","volume":"55","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5177-8248","authenticated-orcid":true,"given":"Naruhiko","family":"Kamogawa","sequence":"first","affiliation":[{"name":"Department of Cerebrovascular Medicine, National Cerebral and Cardiovascular Center, Suita, Japan (N.K., K.M., K.T., M.I., S.Y., M.K.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7948-3636","authenticated-orcid":true,"given":"Kaori","family":"Miwa","sequence":"additional","affiliation":[{"name":"Department of Cerebrovascular Medicine, National Cerebral and Cardiovascular Center, Suita, Japan (N.K., K.M., K.T., M.I., S.Y., M.K.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8346-9845","authenticated-orcid":true,"given":"Kazunori","family":"Toyoda","sequence":"additional","affiliation":[{"name":"Department of Cerebrovascular Medicine, National Cerebral and Cardiovascular Center, Suita, Japan (N.K., K.M., K.T., M.I., S.Y., M.K.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7793-0941","authenticated-orcid":true,"given":"M\u00e4rit","family":"Jensen","sequence":"additional","affiliation":[{"name":"Klinik und Poliklinik f\u00fcr Neurologie, Kopf- und Neurozentrum, Universit\u00e4tsklinikum Hamburg-Eppendorf, Germany (M.J., C.G., G.T.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5228-6643","authenticated-orcid":true,"given":"Manabu","family":"Inoue","sequence":"additional","affiliation":[{"name":"Department of Cerebrovascular Medicine, National Cerebral and Cardiovascular Center, Suita, Japan (N.K., K.M., K.T., M.I., S.Y., M.K.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4751-3538","authenticated-orcid":true,"given":"Sohei","family":"Yoshimura","sequence":"additional","affiliation":[{"name":"Department of Cerebrovascular Medicine, National Cerebral and Cardiovascular Center, Suita, Japan (N.K., K.M., K.T., M.I., S.Y., M.K.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0922-4417","authenticated-orcid":true,"given":"Mayumi","family":"Fukuda-Doi","sequence":"additional","affiliation":[{"name":"Center for Advancing Clinical and Translational Sciences, National Cerebral, and Cardiovascular Center, Suita, Japan (M.F.-D.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takanari","family":"Kitazono","sequence":"additional","affiliation":[{"name":"Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan (T.K.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florent","family":"Boutitie","sequence":"additional","affiliation":[{"name":"Hospices Civils de Lyon, Service de Biostatistique, France (F.B.)."},{"name":"Villeurbanne, France; Laboratoire de Biom\u00e9trie et Biologie Evolutive, Equipe Biostatistique-Sant\u00e9, Villeurbanne, France (F.B.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henry","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Medicine, School of Clinical Sciences, Monash University, Melbourne, VIC, Australia (H.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5473-8671","authenticated-orcid":true,"given":"Peter","family":"Ringleb","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of Heidelberg, Germany (P.R., W.H.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5509-9461","authenticated-orcid":true,"given":"Ona","family":"Wu","sequence":"additional","affiliation":[{"name":"Athinoula A Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Charlestown (O.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0592-9145","authenticated-orcid":true,"given":"Lee H.","family":"Schwamm","sequence":"additional","affiliation":[{"name":"Department of Neurology, Massachusetts General Hospital, Boston (L.H.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3125-7979","authenticated-orcid":true,"given":"Steven","family":"Warach","sequence":"additional","affiliation":[{"name":"Dell Medical School, University of Texas at Austin (S.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6951-6182","authenticated-orcid":true,"given":"Werner","family":"Hacke","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of Heidelberg, Germany (P.R., W.H.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0962-2300","authenticated-orcid":true,"given":"Stephen M.","family":"Davis","sequence":"additional","affiliation":[{"name":"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.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6324-3403","authenticated-orcid":true,"given":"Geoffrey A.","family":"Donnan","sequence":"additional","affiliation":[{"name":"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.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6484-8882","authenticated-orcid":true,"given":"Christian","family":"Gerloff","sequence":"additional","affiliation":[{"name":"Klinik und Poliklinik f\u00fcr Neurologie, Kopf- und Neurozentrum, Universit\u00e4tsklinikum Hamburg-Eppendorf, Germany (M.J., C.G., G.T.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4785-1449","authenticated-orcid":true,"given":"G\u00f6tz","family":"Thomalla","sequence":"additional","affiliation":[{"name":"Klinik und Poliklinik f\u00fcr Neurologie, Kopf- und Neurozentrum, Universit\u00e4tsklinikum Hamburg-Eppendorf, Germany (M.J., C.G., G.T.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6758-4026","authenticated-orcid":true,"given":"Masatoshi","family":"Koga","sequence":"additional","affiliation":[{"name":"Department of Cerebrovascular Medicine, National Cerebral and Cardiovascular Center, Suita, Japan (N.K., K.M., K.T., M.I., S.Y., M.K.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bastian","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Bendszus","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Bladin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leonid","family":"Churilov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brunce","family":"Campbell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Parsons","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nawaf","family":"Yassi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Ebinger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias","family":"Endres","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jochen B.","family":"Fiebach","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy","family":"Kleinig","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lawrence","family":"Latour","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robin","family":"Lemmens","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Levi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Didier","family":"Leys","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos","family":"Molina","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keith","family":"Muir","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norbert","family":"Nighoghossian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salvador","family":"Pedraza","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter D.","family":"Schellinger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Schwab","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claus Z.","family":"Simonsen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shlee S.","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincent","family":"Thijs","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danilo","family":"Toni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chung Y.","family":"Hsu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nils","family":"Wahlgren","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.str.0000014585.17714.67"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e318219fb30"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1177\/1747493015616513"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1007\/s13760-017-0830-7"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jstrokecerebrovasdis.2021.105842"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(11)70192-2"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.str.30.10.2043"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1804355"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.120.030848"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(20)32163-2"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(19)31053-0"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1161\/STR.0000000000000211"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1177\/2396987321989865"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1177\/17474930221090347"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1177\/23969873221089800"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.119.028127"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1813046"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1177\/1747493019840938"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.122.039086"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(07)60149-4"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2015.3656"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1159\/000278929"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.str.29.5.992"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.smrv.2019.101212"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1159\/000091545"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jstrokecerebrovasdis.2011.10.003"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1177\/17474930211059608"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.113.002133"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000011449"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1177\/0271678X221111852"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.108.521583"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.119.028160"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2348-z"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(14)60584-5"}],"container-title":["Stroke"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/STROKEAHA.123.043358","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,9,20]],"date-time":"2024-09-20T15:06:09Z","timestamp":1726844769000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/STROKEAHA.123.043358"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,4]]},"references-count":34,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2024,4]]}},"alternative-id":["10.1161\/STROKEAHA.123.043358"],"URL":"https:\/\/doi.org\/10.1161\/strokeaha.123.043358","relation":{},"ISSN":["0039-2499","1524-4628"],"issn-type":[{"value":"0039-2499","type":"print"},{"value":"1524-4628","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,4]]},"assertion":[{"value":"2023-03-25","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-11-12","order":1,"name":"revised","label":"Revised","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-11-29","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-03-08","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}