• Urs Fischer, Masatoshi Koga, Daniel Strbian, Mattia Branca, Stefanie Abend, Sven Trelle, Maurizio Paciaroni, Götz Thomalla, Patrik Michel, Krassen Nedeltchev, Leo H Bonati, George Ntaios, Thomas Gattringer, Else-Charlotte Sandset, Peter Kelly, Robin Lemmens, P N Sylaja, Diana Aguiar de Sousa, Natan M Bornstein, Zuzana Gdovinova, Takeshi Yoshimoto, Marjaana Tiainen, Helen Thomas, Manju Krishnan, Gek C Shim, Christoph Gumbinger, Jochen Vehoff, Liqun Zhang, Kosuke Matsuzono, Espen Kristoffersen, Philippe Desfontaines, Peter Vanacker, Angelika Alonso, Yusuke Yakushiji, Caterina Kulyk, Dimitri Hemelsoet, Sven Poli, Paiva NunesAnaAFrom the Department of Neurology, University Hospital Basel, University of Basel, Basel (U.F., T.K.), the Department of Neurology (U.F., S.A., K.N., M.G., M.A., C. Ferrari, S.B., C.B., D.J.S., T.H.), the Support Center for Advanced Neuroima, Nicoletta Caracciolo, Peter Slade, Jelle Demeestere, Alexander Salerno, Markus Kneihsl, Timo Kahles, Daria Giudici, Kanta Tanaka, Silja Räty, Rea Hidalgo, David J Werring, Martina Göldlin, Marcel Arnold, Cecilia Ferrari, Seraina Beyeler, Christian Fung, Bruno J Weder, Turgut Tatlisumak, Sabine Fenzl, Beata Rezny-Kasprzak, Arsany Hakim, Georgia Salanti, Claudio Bassetti, Jan Gralla, David J Seiffge, Thomas Horvath, Jesse Dawson, and ELAN Investigators.
• From the Department of Neurology, University Hospital Basel, University of Basel, Basel (U.F., T.K.), the Department of Neurology (U.F., S.A., K.N., M.G., M.A., C. Ferrari, S.B., C.B., D.J.S., T.H.), the Support Center for Advanced Neuroimaging, Institute of Diagnostic and Interventional Neuroradiology (B.J.W.), and the Institute for Diagnostic and Interventional Neuroradiology (S.F., B.R.-K., A.H., J.G.), University Hospital Bern, and CTU Bern (M.B., S.T.), Institute of Social and Preventive Medicine (G.S.), University of Bern, Bern, the Department of Neurology, University Hospital Lausanne, University of Lausanne, Lausanne (P.M., A.S.), the Department of Neurology, Cantonal Hospital Aarau, Aarau (K.N., T.K.), the Research Department, Reha Rheinfelden, Rheinfelden (L.H.B.), and the Department of Neurology, Cantonal Hospital St. Gallen, St. Gallen (J.V.) - all in Switzerland; the Departments of Cerebrovascular Medicine (M. Koga, K.T.) and Neurology (T.Y.), National Cerebral and Cardiovascular Center, Osaka, the Division of Neurology, Department of Medicine, Jichi Medical University, Tochigi (K.M.), and the Department of Neurology, Kansai Medical University, Hirakata (Y.Y.) - all in Japan; the Department of Neurology, Helsinki University Hospital, and University of Helsinki, Helsinki (D.S., M.T., S.R.); Internal, Vascular, and Emergency Medicine, Stroke Unit, Santa Maria della Misericordia Hospital, University of Perugia, Perugia (M.P., D.G.), and the Department of Human Neurosciences, University La Sapienza, Rome (N.C.) - both in Italy; the Department of Neurology, University Medical Center Hamburg-Eppendorf, Hamburg (G.T.), the Department of Neurology, Heidelberg University Hospital (C.G.), and the Department of Neurology, Medical Faculty Mannheim, University of Heidelberg (A.A.), Heidelberg, the Department of Neurology and Stroke and the Hertie Institute for Clinical Brain Research, Tübingen University, Tübingen (S.P.), and the Department of Neurosurgery, Medical Center, University of Freiburg, Freiburg (C. Fung) - all in Germany; the Department of Internal Medicine, Faculty of Medicine, School of Health Sciences, University of Thessaly, Larissa, Greece (G.N.); the Department of Neurology, and the Division of Neuroradiology, Vascular and Interventional Radiology, Department of Radiology, Medical University of Graz, Graz (T.G., M. Kneihsl), and the Department of Neurology 2, Kepler University Hospital, Johannes Kepler University, Linz (C.K.) - both in Austria; the Department of Neurology, Oslo University Hospital (E.-C.S.), the Department of General Practice, University of Oslo (E.K.), and the Norwegian Air Ambulance Foundation (E.-C.S.), Oslo, and the Department of Neurology, Akershus University Hospital, Lørenskog (E.K.) - all in Norway; the Department of Neurology, Mater Misericordiae University Hospital, Dublin (P.K.); KU Leuven, Department of Neurosciences, Experimental Neurology, and the Department of Neurology, University Hospitals Leuven, Leuven (R.L., J. Demeestere), the Department of Neurology, Comprehensive Stroke Unit, CHC MontLégia Hospital, Liège (P.D.), the Department of Neurology, Algemeen Ziekenhuis Groeninge Kortrijk, Kortrijk (P.V.), the Neurovascular Center and Stroke Unit Antwerp, Antwerp University Hospital, and the Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp (P.V.), and the Department of Neurology, Ghent University Hospital, Ghent (D.H.) - all in Belgium; Sree Chitra Tirunal Institute for Medical Sciences and Technology, Thiruvananthapuram, India (P.N.S.); the Stroke Center, Lisbon Central University Hospital (D.A.S., A.P.N.) and Faculty of Medicine, University of Lisbon (D.A.S.) - both in Lisbon, Portugal; the Department of Neurology, Shaare Zedek Medical Center, Jerusalem (N.M.B.); the Department of Neurology, Faculty of Medicine, Pavol Jozef Safarik University, and University Hospital Louis Pasteur - both in Košice, Slovakia (Z.G.); Glan Clwyd Hospital, Betsi Cadwaladr University Health Board, Rhyl (H.T., R.H.), the Stroke Unit, Morriston Hospital, Swansea Bay University Health Board, Swansea (M. Krishnan, P.S.), the Stroke Department, University Hospital of North Durham, Durham (G.C.S.), the Department of Neurology, St. George's University Hospital (L.Z.), and the Stroke Research Centre, Department of Brain Repair and Rehabilitation, University College London Queen Square Institute of Neurology, University College London (D.J.W.), London, and the School of Cardiovascular and Metabolic Health, University of Glasgow, Glasgow (J. Dawson) - all in the United Kingdom; and the Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, and the Department of Neurology, Sahlgrenska University Hospital - both in Gothenburg, Sweden (T.T.).
• N. Engl. J. Med. 2023 Jun 29; 388 (26): 241124212411-2421.

BackgroundThe effect of early as compared with later initiation of direct oral anticoagulants (DOACs) in persons with atrial fibrillation who have had an acute ischemic stroke is unclear.MethodsWe performed an investigator-initiated, open-label trial at 103 sites in 15 countries. Participants were randomly assigned in a 1:1 ratio to early anticoagulation (within 48 hours after a minor or moderate stroke or on day 6 or 7 after a major stroke) or later anticoagulation (day 3 or 4 after a minor stroke, day 6 or 7 after a moderate stroke, or day 12, 13, or 14 after a major stroke). Assessors were unaware of the trial-group assignments. The primary outcome was a composite of recurrent ischemic stroke, systemic embolism, major extracranial bleeding, symptomatic intracranial hemorrhage, or vascular death within 30 days after randomization. Secondary outcomes included the components of the composite primary outcome at 30 and 90 days.ResultsOf 2013 participants (37% with minor stroke, 40% with moderate stroke, and 23% with major stroke), 1006 were assigned to early anticoagulation and 1007 to later anticoagulation. A primary-outcome event occurred in 29 participants (2.9%) in the early-treatment group and 41 participants (4.1%) in the later-treatment group (risk difference, -1.18 percentage points; 95% confidence interval [CI], -2.84 to 0.47) by 30 days. Recurrent ischemic stroke occurred in 14 participants (1.4%) in the early-treatment group and 25 participants (2.5%) in the later-treatment group (odds ratio, 0.57; 95% CI, 0.29 to 1.07) by 30 days and in 18 participants (1.9%) and 30 participants (3.1%), respectively, by 90 days (odds ratio, 0.60; 95% CI, 0.33 to 1.06). Symptomatic intracranial hemorrhage occurred in 2 participants (0.2%) in both groups by 30 days.ConclusionsIn this trial, the incidence of recurrent ischemic stroke, systemic embolism, major extracranial bleeding, symptomatic intracranial hemorrhage, or vascular death at 30 days was estimated to range from 2.8 percentage points lower to 0.5 percentage points higher (based on the 95% confidence interval) with early than with later use of DOACs. (Funded by the Swiss National Science Foundation and others; ELAN ClinicalTrials.gov number, NCT03148457.).Copyright © 2023 Massachusetts Medical Society.

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