{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T05:18:14Z","timestamp":1780636694213,"version":"3.54.1"},"reference-count":33,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2026,1,2]],"date-time":"2026-01-02T00:00:00Z","timestamp":1767312000000},"content-version":"vor","delay-in-days":1,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004362","name":"Schweizerische Herzstiftung","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004362","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Intramural Research Fund for Cardiovascular Diseases of the National Cerebral and Cardiovascular Center, Japan","award":["20-4-5"],"award-info":[{"award-number":["20-4-5"]}]},{"DOI":"10.13039\/501100001711","name":"Schweizerischer Nationalfonds zur F\u00f6rderung der Wissenschaftlichen Forschung","doi-asserted-by":"publisher","award":["32003B_169975"],"award-info":[{"award-number":["32003B_169975"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001711","name":"Schweizerischer Nationalfonds zur F\u00f6rderung der Wissenschaftlichen Forschung","doi-asserted-by":"publisher","award":["32003B_197009"],"award-info":[{"award-number":["32003B_197009"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000364","name":"Stroke Association","doi-asserted-by":"publisher","award":["2017\/02"],"award-info":[{"award-number":["2017\/02"]}],"id":[{"id":"10.13039\/501100000364","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Whether the risk-benefit profile of once-daily versus twice-daily direct oral anticoagulants (DOAC) differs after atrial fibrillation(AF)-associated ischemic stroke is unclear. We explored this in a post-hoc analysis of ELAN trial data (NCT03148457).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Patients and methods<\/jats:title>\n                    <jats:p>We compared the risk of the primary outcome (recurrent ischemic stroke, systemic embolism, intracranial hemorrhage (ICH), major extracranial bleeding, vascular death) from treatment initiation to the trial\u2019s 90-day follow-up in participants treated with once-daily or twice-daily DOAC after AF-associated stroke using Firth\u2019s logistic and Cox proportional hazards regression in unadjusted, inverse-probability-of-treatment-weighted and augmented-inverse-probability-weighted models to address confounding. Secondary outcomes were the primary outcome components and non-major bleeding. We calculated the net clinical benefit (NCB) of twice-daily over once-daily DOAC by subtracting the weighted rate of excess bleeding attributable to twice-daily DOAC from the rate of excess ischemic events possibly prevented by twice-daily DOAC.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We analyzed 1890\/2013 (94%) participants (median age 77 years, 45% female), of whom 384 (20%) received once-daily and 1506 (80%) twice-daily DOAC. The primary outcome occurred in 64 (3.4%) participants, and did not differ between DOAC types in logistic (ORunadjusted 0.89 (95% CI 0.50\u20131.66); ORweighted 1.34 (0.71\u20132.79); ORaugmented 1.45 (0.81\u20133.21); twice-daily vs once-daily DOAC) nor in Cox models. We identified no clear differences in any secondary outcome. NCB analysis revealed a near-neutral net effect of twice-daily versus once-daily DOAC (+0.28 to +0.67 weighted events possibly prevented\/100 person-months for ICH weights 1.5\u20133.3).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion and conclusion<\/jats:title>\n                    <jats:p>The risk-benefit profile of once-daily versus twice-daily DOAC after AF-associated ischemic stroke does not seem to differ.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/esj\/23969873251360974","type":"journal-article","created":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T11:01:36Z","timestamp":1768906896000},"source":"Crossref","is-referenced-by-count":1,"title":["Once- versus twice-daily direct oral anticoagulants after ischemic stroke in atrial fibrillation \u2013 A post-hoc analysis of the ELAN trial"],"prefix":"10.1093","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9475-2208","authenticated-orcid":false,"given":"Alexandros A","family":"Polymeris","sequence":"first","affiliation":[{"name":"Department of Neurology and Stroke Center , University Hospital Basel and University of Basel, Basel ,","place":["Switzerland"]},{"name":"Stroke Division , Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5803-3233","authenticated-orcid":false,"given":"Jean-Beno\u00eet","family":"Rossel","sequence":"additional","affiliation":[{"name":"Department of Clinical Research , University of Bern, Bern ,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masatoshi","family":"Koga","sequence":"additional","affiliation":[{"name":"Department of Cerebrovascular Medicine , National Cerebral and Cardiovascular Center, Suita ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9095-2344","authenticated-orcid":false,"given":"Daniel","family":"Strbian","sequence":"additional","affiliation":[{"name":"Department of Neurology , Helsinki University Hospital, Helsinki ,","place":["Finland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adhiyaman","family":"Vedamurthy","sequence":"additional","affiliation":[{"name":"Glan Clwyd Hospital , Betsi Cadwaladr University Local Health Board, Rhyl ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manju","family":"Krishnan","sequence":"additional","affiliation":[{"name":"Stroke Unit , Morriston Hospital, Swansea Bay University Health Board, Swansea ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mattia","family":"Branca","sequence":"additional","affiliation":[{"name":"Department of Clinical Research , University of Bern, Bern ,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0647-9273","authenticated-orcid":false,"given":"Thomas","family":"Meinel","sequence":"additional","affiliation":[{"name":"Department of Neurology , Inselspital, Bern University Hospital and University of Bern, Bern ,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8999-5424","authenticated-orcid":false,"given":"Espen Saxhaug","family":"Kristoffersen","sequence":"additional","affiliation":[{"name":"Department of General Practice , University of Oslo, Oslo ,","place":["Norway"]},{"name":"Department of Neurology , Akershus University Hospital, L\u00f8renskog ,","place":["Norway"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3178-8171","authenticated-orcid":false,"given":"Takeshi","family":"Yoshimoto","sequence":"additional","affiliation":[{"name":"Department of Neurology , National Cerebral and Cardiovascular Center, Suita ,","place":["Japan"]},{"name":"Department of Stroke and Cerebrovascular Diseases , University of Tsukuba Hospital, Tsukuba ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3291-5083","authenticated-orcid":false,"given":"Kanta","family":"Tanaka","sequence":"additional","affiliation":[{"name":"Department of Cerebrovascular Medicine , National Cerebral and Cardiovascular Center, Suita ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takenobu","family":"Kunieda","sequence":"additional","affiliation":[{"name":"Department of Neurology , Kansai Medical University, Hirakata 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,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8186-0237","authenticated-orcid":false,"given":"Jelle","family":"Demeestere","sequence":"additional","affiliation":[{"name":"KU Leuven , Department of Neurosciences, Experimental Neurology, and the Department of Neurology, University Hospitals Leuven, Leuven ,","place":["Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8494-5527","authenticated-orcid":false,"given":"Alexander","family":"Salerno","sequence":"additional","affiliation":[{"name":"Department of Neurology , University Hospital Lausanne, University of Lausanne, Lausanne ,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicoletta G","family":"Caracciolo","sequence":"additional","affiliation":[{"name":"Department of Human Neurosciences , University La Sapienza, Rome 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