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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>\n                      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 (OR\n                      <jats:sub>unadjusted<\/jats:sub>\n                      0.89 (95% CI 0.50\u20131.66); OR\n                      <jats:sub>weighted<\/jats:sub>\n                      1.34 (0.71\u20132.79); OR\n                      <jats:sub>augmented<\/jats:sub>\n                      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).\n                    <\/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":"10.1177\/23969873251360974","type":"journal-article","created":{"date-parts":[[2025,8,11]],"date-time":"2025-08-11T09:42:21Z","timestamp":1754905341000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"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","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, Switzerland"},{"name":"Stroke Division, Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"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, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masatoshi","family":"Koga","sequence":"additional","affiliation":[{"name":"Department of Cerebrovascular Medicine, National Cerebral and Cardiovascular Center, Suita, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"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, Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adhiyaman","family":"Vedamurthy","sequence":"additional","affiliation":[{"name":"Glan Clwyd Hospital, Betsi Cadwaladr University Local Health Board, Rhyl, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manju","family":"Krishnan","sequence":"additional","affiliation":[{"name":"Stroke Unit, Morriston Hospital, Swansea Bay University Health Board, Swansea, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mattia","family":"Branca","sequence":"additional","affiliation":[{"name":"Department of Clinical Research, University of Bern, Bern, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"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, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"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, Norway"},{"name":"Department of Neurology, Akershus University Hospital, L\u00f8renskog, Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"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 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T","family":"Engelter","sequence":"additional","affiliation":[{"name":"Department of Neurology and Stroke Center, University Hospital Basel and University of Basel, Basel, Switzerland"},{"name":"Department of Rehabilitation and Neurology, University Department of Geriatric Medicine FELIX PLATTER, University of Basel, Basel, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elias","family":"Auer","sequence":"additional","affiliation":[{"name":"Department of Neurology, Inselspital, Bern University Hospital and University of Bern, Bern, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas","family":"Horvath","sequence":"additional","affiliation":[{"name":"Department of Neurology, Inselspital, Bern University Hospital and University of Bern, Bern, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3890-3849","authenticated-orcid":false,"given":"David 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