{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T16:01:43Z","timestamp":1791475303870,"version":"4.3.4"},"reference-count":31,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T00:00:00Z","timestamp":1776902400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T00:00:00Z","timestamp":1776902400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Annals of Neurology"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>The benefit of intravenous thrombolysis (IVT) before endovascular treatment (EVT) in patients with acute ischemic stroke due to large vessel occlusion (LVO) who present directly to EVT\u2010capable centers remains uncertain, and the effect may differ according to underlying stroke etiology. We assessed whether the benefit of IVT plus EVT versus EVT alone varied by stroke etiologies (large\u2010artery atherosclerosis, cardioembolism, or other\/undetermined).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We performed an individual participant data meta\u2010analysis of 6 randomized controlled trials (RCTs) that compared IVT plus EVT to EVT alone in patients with LVO within 4.5\u2009hours of stroke onset or time last known well. The heterogeneity of treatment effect was assessed using ordinal logistic regression models with interaction terms for stroke etiology and treatment in the intention\u2010to\u2010treat population, followed by subsequent mixed\u2010effects meta\u2010analysis. An additional analysis was performed to assess whether the treatment effect of IVT plus EVT differed by atrial fibrillation status.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Among 2,313 eligible patients from 6 RCTs, 1,160 were randomized to the IVT plus EVT group and 1,153 to the EVT alone group. Median age was 71\u2009years (interquartile range [IQR] =\u200962\u201378\u2009years), and 44.3% of patients were women. Stroke etiology was classified as cardioembolism in 977 of 2,313 patients (42%), large artery atherosclerosis in 430 (19%), and other or unknown\/undetermined in 906 (39%). No evidence of treatment effect modification by stroke etiologies on the association between IVT and 90\u2010day functional outcome was observed (\n                      <jats:italic>P<\/jats:italic>\n                      for interaction\u2009=\u20090.60). For patients with other\/undetermined stroke etiology, IVT plus EVT was associated with better 90\u2010day functional prognosis (adjusted common odds ratio for a lower level of disability\u2009=\u20091.34, 95% confidence interval [CI] =\u20091.05\u20131.69). No treatment effect modification by stroke etiology was found for safety outcomes. No treatment effect heterogeneity by atrial fibrillation was found for all outcomes.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Interpretation<\/jats:title>\n                    <jats:p>Among patients with LVO presenting directly to EVT\u2010capable centers, stroke etiologies do not modify the overall efficacy or safety of IVT before EVT. The isolated benefit observed in the other\/undetermined subgroup requires confirmation. ANN NEUROL 2026;100:180\u2013190<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ana.78225","type":"journal-article","created":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T04:25:02Z","timestamp":1777004702000},"page":"180-190","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Stroke Etiologies With Intravenous Thrombolysis before Thrombectomy and Functional Outcomes in Anterior Circulation Large Vessel Occlusion"],"prefix":"10.1002","volume":"100","author":[{"given":"Changwei","family":"Guo","sequence":"first","affiliation":[{"name":"Department of Neurology Xinqiao Hospital and The Second Affiliated Hospital, Army Medical University (Third Military Medical University)  Chongqing People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabiano","family":"Cavalcante","sequence":"additional","affiliation":[{"name":"Department of Radiology and Nuclear Medicine Amsterdam University Medical Centres, University of Amsterdam, Amsterdam Neuroscience  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-9628-4938","authenticated-orcid":false,"given":"Shihai","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Neurology Xinqiao Hospital and The Second Affiliated Hospital, Army Medical University (Third Military Medical University)  Chongqing People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kentaro","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Department of Neurology Nippon Medical School  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kilian","family":"Treurniet","sequence":"additional","affiliation":[{"name":"Department of Radiology and Nuclear Medicine Amsterdam University Medical Centres, University of Amsterdam, Amsterdam Neuroscience  Amsterdam The Netherlands"},{"name":"Department of Radiology Haaglanden Medical Centre  The Hague The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannes","family":"Kaesmacher","sequence":"additional","affiliation":[{"name":"University Institute of Diagnostic and Interventional Neuroradiology, University Hospital of Bern, University of Bern  Bern Switzerland"},{"name":"Diagnostic and Interventional Neuroradiology, CIC\u2010IT 1415, CHRU de Tours  Tours France"},{"name":"Le Studium Loire Valley Institute for Advanced Studies  Tours France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manon","family":"Kappelhof","sequence":"additional","affiliation":[{"name":"Department of Radiology and Nuclear Medicine Amsterdam University Medical Centres, University of Amsterdam, Amsterdam Neuroscience  Amsterdam The Netherlands"},{"name":"Department of Radiology Onze Lieve Vrouwe Gasthuis (OLVG) Hospital  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roman","family":"Rohner","sequence":"additional","affiliation":[{"name":"University Institute of Diagnostic and Interventional Neuroradiology, University Hospital of Bern, University of Bern  Bern Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1945-2360","authenticated-orcid":false,"given":"Jiaxing","family":"Song","sequence":"additional","affiliation":[{"name":"The Second Affiliated Hospital of Chongqing Medical University  Chongqing People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pengfei","family":"Yang","sequence":"additional","affiliation":[{"name":"Neurovascular Centre, Naval Medical University Changhai Hospital  Shanghai People's Republic of China"},{"name":"Oriental PanVascular Devices Innovations College, University of Shanghai for Science and Technology  Shanghai People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-2463-2826","authenticated-orcid":false,"given":"Xiaolei","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Neurology Xinqiao Hospital and The Second Affiliated Hospital, Army Medical University (Third Military Medical University)  Chongqing People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gaoming","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Neurology Xinqiao Hospital and The Second Affiliated Hospital, Army Medical University (Third Military Medical University)  Chongqing People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xu","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Neurology Xinqiao Hospital and The Second Affiliated Hospital, Army Medical University (Third Military Medical University)  Chongqing People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinfu","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Neurology Xinqiao Hospital and The Second Affiliated Hospital, Army Medical University (Third Military Medical University)  Chongqing People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-7220-2504","authenticated-orcid":false,"given":"Lilan","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Neurology Xinqiao Hospital and The Second Affiliated Hospital, Army Medical University (Third Military Medical University)  Chongqing People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianmin","family":"Liu","sequence":"additional","affiliation":[{"name":"Neurovascular Centre, Naval Medical University Changhai Hospital  Shanghai People's Republic of China"},{"name":"Oriental PanVascular Devices Innovations College, University of Shanghai for Science and Technology  Shanghai People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linyu","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Neurology Xinqiao Hospital and The Second Affiliated Hospital, Army Medical University (Third Military Medical University)  Chongqing People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pengfei","family":"Xing","sequence":"additional","affiliation":[{"name":"Department of Radiology Onze Lieve Vrouwe Gasthuis (OLVG) Hospital  Amsterdam The Netherlands"},{"name":"Neurovascular Centre, Naval Medical University Changhai Hospital  Shanghai People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernard","family":"Yan","sequence":"additional","affiliation":[{"name":"Melbourne Brain Centre, Royal Melbourne Hospital, University of Melbourne  Parkville Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chang","family":"Liu","sequence":"additional","affiliation":[{"name":"The Second Affiliated Hospital of Chongqing Medical University  Chongqing People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5559-6292","authenticated-orcid":false,"given":"Lei","family":"Zhang","sequence":"additional","affiliation":[{"name":"Neurovascular Centre, Naval Medical University Changhai Hospital  Shanghai People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongwei","family":"Zhang","sequence":"additional","affiliation":[{"name":"Neurovascular Centre, Naval Medical University Changhai Hospital  Shanghai People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kendal","family":"Redmond","sequence":"additional","affiliation":[{"name":"Interventional Neuroradiology Gold Coast University Hospital  Southport Queensland Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Zhou","sequence":"additional","affiliation":[{"name":"Neurovascular Centre, Naval Medical University Changhai Hospital  Shanghai People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Mitchell","sequence":"additional","affiliation":[{"name":"Interventional Neuroradiology Gold Coast University Hospital  Southport Queensland Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3594-2159","authenticated-orcid":false,"given":"Mirjam R.","family":"Heldner","sequence":"additional","affiliation":[{"name":"Department of Radiology Royal Melbourne Hospital, University of Melbourne  Parkville Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hester","family":"Lingsma","sequence":"additional","affiliation":[{"name":"Department of Public Health Erasmus Medical Centre  Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Gralla","sequence":"additional","affiliation":[{"name":"University Institute of Diagnostic and Interventional Neuroradiology, University Hospital of Bern, University of Bern  Bern Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0521-4051","authenticated-orcid":false,"given":"Urs","family":"Fischer","sequence":"additional","affiliation":[{"name":"Department of Neurology Inselspital, Bern University Hospital, and University of Bern  Bern Bern Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yvo","family":"Roos","sequence":"additional","affiliation":[{"name":"Department of Neurology Amsterdam University Medical Centres, University of Amsterdam, Amsterdam Neuroscience  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fengli","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Neurology Xinqiao Hospital and The Second Affiliated Hospital, Army Medical University (Third Military Medical University)  Chongqing People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raul G.","family":"Nogueira","sequence":"additional","affiliation":[{"name":"UPMC Stroke Institute, Departments of Neurology and Neurosurgery University of Pittsburgh Medical Centre  Pittsburgh PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thanh","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Department of Neurology, Neurosurgery, and Radiology Boston Medical Centre  Boston MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey","family":"Saver","sequence":"additional","affiliation":[{"name":"Department of Neurology David Geffen School of Medicine at UCLA  Los Angeles CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles","family":"Majoie","sequence":"additional","affiliation":[{"name":"Department of Radiology and Nuclear Medicine Amsterdam University Medical Centres, University of Amsterdam, Amsterdam Neuroscience  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazumi","family":"Kimura","sequence":"additional","affiliation":[{"name":"Department of Neurology Nippon Medical School  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6323-2659","authenticated-orcid":false,"given":"Wenjie","family":"Zi","sequence":"additional","affiliation":[{"name":"Department of Neurology Xinqiao Hospital and The Second Affiliated Hospital, Army Medical University (Third Military Medical University)  Chongqing People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2596-2631","authenticated-orcid":false,"given":"Qingwu","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Neurology Xinqiao Hospital and The Second Affiliated Hospital, Army Medical University (Third Military Medical University)  Chongqing People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"for the IRIS Investigators","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,4,23]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2001123"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2020.23523"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2020.23522"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2107727"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(22)00537-2"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(22)00564-5"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(23)01142-X"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2024.0589"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.120.030796"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.24.1.35"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1468-1331.2012.03790.x"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.124.047092"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.122.038563"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1136\/neurintsurg-2021-018275"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/ene.16453"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1136\/neurintsurg-2020-016720"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(22)01054-6"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1716405"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1177\/17474930231162265"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000207535"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.122.040008"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.119.026299"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.119.027749"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jns.2016.11.006"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2503867"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41582-022-00663-4"},{"key":"e_1_2_12_28_1","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.108.532812"},{"key":"e_1_2_12_29_1","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.116.012865"},{"key":"e_1_2_12_30_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00508-020-01727-5"},{"key":"e_1_2_12_31_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2020.5697"},{"key":"e_1_2_12_32_1","first-page":"783","article-title":"Summary of the Chinese stroke prevention and treatment report 2021","volume":"20","author":"Group ROSP","year":"2023","journal-title":"Chin J Cerebrovasc Dis"}],"container-title":["Annals of Neurology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ana.78225","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ana.78225","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ana.78225","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T02:36:11Z","timestamp":1790044571000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ana.78225"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,23]]},"references-count":31,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026,7]]}},"alternative-id":["10.1002\/ana.78225"],"URL":"https:\/\/doi.org\/10.1002\/ana.78225","archive":["Portico"],"relation":{},"ISSN":["0364-5134","1531-8249"],"issn-type":[{"value":"0364-5134","type":"print"},{"value":"1531-8249","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,23]]},"assertion":[{"value":"2025-12-10","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-03-19","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-04-23","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}