{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T22:35:55Z","timestamp":1789684555566,"version":"4.0.1"},"reference-count":25,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","funder":[{"DOI":"10.13039\/501100001711","name":"Swiss National Science Foundation","doi-asserted-by":"crossref","award":["32003B_197009"],"award-info":[{"award-number":["32003B_197009"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001711","name":"Swiss National Science Foundation","doi-asserted-by":"crossref","award":["32003B_169975"],"award-info":[{"award-number":["32003B_169975"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100004362","name":"Schweizerische Herzstiftung","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100004362","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Stroke Association in the United Kingdom","award":["2017\/02"],"award-info":[{"award-number":["2017\/02"]}]},{"name":"Intramural Research Fund for Cardiovascular Diseases of the National Cerebral and Cardiovascular Center","award":["20-4-5"],"award-info":[{"award-number":["20-4-5"]}]},{"name":"Swiss Academy of Medical Sciences\/Bangerter-Rhyner Foundation","award":["YTCR_13\/18"],"award-info":[{"award-number":["YTCR_13\/18"]}]}],"content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[2024,7,2]]},"abstract":"<jats:sec>\n            <jats:title>BACKGROUND:<\/jats:title>\n            <jats:p>Whether hemorrhagic transformation (HT) modifies the treatment effect of early compared with late initiation of direct oral anticoagulation in people with ischemic stroke and atrial fibrillation is unknown.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>METHODS:<\/jats:title>\n            <jats:p>This is a post hoc analysis of the ELAN trial (Early Versus Late Initiation of Direct Oral Anticoagulants in Post-Ischaemic Stroke Patients With Atrial Fibrillation). The primary outcome was a composite of recurrent ischemic stroke, symptomatic intracranial hemorrhage, major extracranial bleeding, systemic embolism, or vascular death within 30 days. Secondary outcomes were the individual components, 30- and 90-day functional outcome. We estimated outcomes based on HT, subclassified as hemorrhagic infarction (HI) or parenchymal hemorrhage (PH) on prerandomization imaging (core laboratory rating) using adjusted risk differences between treatment arms.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>RESULTS:<\/jats:title>\n            <jats:p>Overall, 247 of 1970 participants (12.5%) had HT (114 HI 1, 77 HI 2, 34 PH 1, 22 PH 2). For the primary outcome, the estimated adjusted risk difference (early versus late) was \u22122.2% (95% CI, \u22127.8% to 3.5%) in people with HT (HI: \u22124.7% [95% CI, \u221210.8% to 1.4%]; PH: 6.1% [95% CI, \u22128.5% to 20.6%]) and \u22120.9% (95% CI, \u22122.6% to 0.8%) in people without HT. Numbers of symptomatic intracranial hemorrhage were identical in people with and without HT. With early treatment, the estimated adjusted risk difference for poor 90-day functional outcome (modified Rankin Scale score, 3\u20136) was 11.5% (95% CI, \u22120.8% to 23.8%) in participants with HT (HI: 7.4% [95% CI, \u22126.4% to 21.2%]; PH: 25.1% [95% CI, 0.2% to 50.0%]) and \u22122.6% (95% CI, \u22127.1% to 1.8%) in people without HT.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>CONCLUSIONS:<\/jats:title>\n            <jats:p>We found no evidence of major treatment effect heterogeneity or safety concerns with early compared with late direct oral anticoagulation initiation in people with and without HT. However, early direct oral anticoagulation initiation may worsen functional outcomes in people with PH.<\/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=\"http:\/\/www.clinicaltrials.gov\">http:\/\/www.clinicaltrials.gov<\/jats:ext-link>\n              ; Unique identifier: NCT03148457.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circulationaha.124.069324","type":"journal-article","created":{"date-parts":[[2024,5,16]],"date-time":"2024-05-16T12:00:50Z","timestamp":1715860850000},"page":"19-29","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":27,"title":["Early Versus Late Initiation of Direct Oral Anticoagulants After Ischemic Stroke in People With Atrial Fibrillation and Hemorrhagic Transformation: Prespecified Subanalysis of the Randomized Controlled ELAN Trial"],"prefix":"10.1161","volume":"150","clinical-trial-number":[{"clinical-trial-number":"nct03148457","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-1331-705X","authenticated-orcid":true,"given":"Roman","family":"Rohner","sequence":"first","affiliation":[{"name":"University Institute of Diagnostic and Interventional Neuroradiology (R.R., A.H., S.F., B.R.-K.), Inselspital Bern University Hospital and University of Bern, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6334-9432","authenticated-orcid":true,"given":"Markus","family":"Kneihsl","sequence":"additional","affiliation":[{"name":"Department of Neurology (M. Kneihsl, T.G.), Medical University of Graz, Austria."},{"name":"Department of Radiology, Division of Neuroradiology, Vascular and Interventional Radiology (M. Kneihsl, T.G.), Medical University of Graz, Austria."},{"name":"Department of Neurology, University and University Hospital Basel, Switzerland (M. Kneihsl, L.B., M. Katan, U.F.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5800-116X","authenticated-orcid":true,"given":"Martina B.","family":"Goeldlin","sequence":"additional","affiliation":[{"name":"Department of Neurology (M.B.G., S.A., T.H., U.F.), Inselspital Bern University Hospital and University of Bern, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9431-1069","authenticated-orcid":true,"given":"Arsany","family":"Hakim","sequence":"additional","affiliation":[{"name":"University Institute of Diagnostic and Interventional Neuroradiology (R.R., A.H., S.F., B.R.-K.), Inselspital Bern University Hospital and University of Bern, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8063-7882","authenticated-orcid":true,"given":"Mattia","family":"Branca","sequence":"additional","affiliation":[{"name":"Department of Clinical Research, University of Bern, Switzerland (M.B., S.T.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-9901-9187","authenticated-orcid":true,"given":"Stefanie","family":"Abend","sequence":"additional","affiliation":[{"name":"Department of Neurology (M.B.G., S.A., T.H., U.F.), Inselspital Bern University Hospital and University of Bern, Switzerland."},{"name":"Department of Clinical Research, University of Bern, Switzerland (M.B., S.T.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6629-3366","authenticated-orcid":true,"given":"Waldo","family":"Valenzuela Pinilla","sequence":"additional","affiliation":[{"name":"Support Center for Advanced Neuroimaging (W.V.P.), Inselspital Bern University Hospital and University of Bern, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabine","family":"Fenzl","sequence":"additional","affiliation":[{"name":"University Institute of Diagnostic and Interventional Neuroradiology (R.R., A.H., S.F., B.R.-K.), Inselspital Bern University Hospital and University of Bern, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beata","family":"Rezny-Kasprzak","sequence":"additional","affiliation":[{"name":"University Institute of Diagnostic and Interventional Neuroradiology (R.R., A.H., S.F., B.R.-K.), Inselspital Bern University Hospital and University of Bern, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9095-2344","authenticated-orcid":true,"given":"Daniel","family":"Strbian","sequence":"additional","affiliation":[{"name":"Department of Neurology, Helsinki University Hospital, and University of Helsinki, Finland (D.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8162-8910","authenticated-orcid":true,"given":"Sven","family":"Trelle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5483-8795","authenticated-orcid":true,"given":"Maurizio","family":"Paciaroni","sequence":"additional","affiliation":[{"name":"Internal, Vascular, and Emergency Medicine, Stroke Unit, Santa Maria della Misericordia Hospital, University of Perugia, Italy (M.P.)."}],"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":"Department of Neurology, University Medical Center Hamburg\u2013Eppendorf, Germany (G.T.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4954-7579","authenticated-orcid":true,"given":"Patrik","family":"Michel","sequence":"additional","affiliation":[{"name":"Department of Neurology, University Hospital Lausanne, University of Lausanne, Switzerland (P.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krassen","family":"Nedeltchev","sequence":"additional","affiliation":[{"name":"Department of Neurology, Cantonal Hospital Aarau, Switzerland (K.N.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6065-6576","authenticated-orcid":true,"given":"Thomas","family":"Gattringer","sequence":"additional","affiliation":[{"name":"Department of Neurology (M. Kneihsl, T.G.), Medical University of Graz, Austria."},{"name":"Department of Radiology, Division of Neuroradiology, Vascular and Interventional Radiology (M. Kneihsl, T.G.), Medical University of Graz, Austria."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4312-4778","authenticated-orcid":true,"given":"Else C.","family":"Sandset","sequence":"additional","affiliation":[{"name":"Department of Neurology, Oslo University Hospital, Norway (E.C.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1163-8133","authenticated-orcid":true,"given":"Leo","family":"Bonati","sequence":"additional","affiliation":[{"name":"Department of Neurology, University and University Hospital Basel, Switzerland (M. Kneihsl, L.B., M. 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