{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T22:17:49Z","timestamp":1793053069849,"version":"4.5.0"},"reference-count":16,"publisher":"American Medical Association (AMA)","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Cardiol"],"published-print":{"date-parts":[[2025,6,1]]},"abstract":"\n Importance<\/jats:title>\n In patients with atrial fibrillation (AF), oral anticoagulants (OACs) reduce the risk of stroke.<\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n To investigate if patients with less prior OAC exposure respond differently to a new OAC than patients with more OAC exposure.<\/jats:p>\n <\/jats:sec>\n \n Design, Setting, and Participants<\/jats:title>\n In this prespecified exploratory subgroup analysis of the Oral Factor 11a Inhibitor Asundexian as Novel Antithrombotic\u2013Atrial Fibrillation (OCEANIC-AF) randomized clinical trial, patients enrolled in the OCEANIC-AF trial were categorized as OAC naive or OAC experienced based on whether they had 6 or fewer weeks or more than 6 weeks of prior OAC use. The effect of asundexian vs apixaban was then compared on outcomes among patients who were OAC naive and OAC experienced. The study setting included 1035 sites in 38 countries, and participants were those enrolled in the OCEANIC-AF trial. Data were analyzed from June to July 2024.<\/jats:p>\n <\/jats:sec>\n \n Interventions<\/jats:title>\n Asundexian, a novel factor XIa inhibitor, was compared with apixaban in patients with AF.<\/jats:p>\n <\/jats:sec>\n \n Main Outcomes and Measures<\/jats:title>\n The primary efficacy outcome was stroke or systemic embolism. The main safety outcome was major bleeding.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Of patients in the OCEANIC-AF trial, 2493 (17%) were OAC naive (mean [SD] age, 72.6 [8.6] years; 1464 male [59%]) and 12\u202f317 (83%) were OAC experienced (mean [SD] age, 74.2 [7.5] years; 8132 male [66%]). In the asundexian arm, patients who were OAC naive had a stroke or systemic embolism rate of 0.8% (10 of 1238) compared with 1.4% (88 of 6177) in those who were OAC experienced. In the apixaban arm, patients who were OAC naive had a stroke or systemic embolism rate of 0.6% (7 of 1255) compared with 0.3% (19 of 6140) in those who were OAC experienced. Thus, patients who were OAC naive had a smaller increase in stroke or systemic embolism with asundexian compared with apixaban (hazard ratio [HR], 1.42; 95% CI, 0.54-3.73) than patients who were OAC experienced (HR, 4.66; 95% CI, 2.84-7.65;\n P<\/jats:italic>\n for interaction\u2009=.03). Bleeding rates were lower among both OAC-naive patients (0.2% [2 of 1228]) and OAC-experienced patients (0.2% [15 of 6145]) assigned asundexian than among OAC-naive patients (1.0% [13 of 1249]) and OAC-experienced patients (0.7% [40 of 6115]) assigned apixaban.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions and Relevance<\/jats:title>\n In the OCEANIC-AF randomized clinical trial, patients with AF who were OAC naive had a smaller increase in stroke or systemic embolism and a similar lower rate of bleeding with asundexian compared with apixaban than patients who were OAC experienced. The mechanism of these findings is unknown and deserves further research.<\/jats:p>\n <\/jats:sec>\n \n Trial Registration<\/jats:title>\n \n ClinicalTrials.gov Identifier:\n NCT05643573<\/jats:ext-link>\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1001\/jamacardio.2025.0277","type":"journal-article","created":{"date-parts":[[2025,3,26]],"date-time":"2025-03-26T11:56:05Z","timestamp":1742990165000},"page":"555","source":"Crossref","is-referenced-by-count":11,"title":["Asundexian or Apixaban in Patients With Atrial Fibrillation According to Prior Oral Anticoagulant Use"],"prefix":"10.1001","volume":"10","author":[{"given":"John H.","family":"Alexander","sequence":"first","affiliation":[{"name":"Duke Clinical Research Institute, Division of Cardiology, Duke University School of Medicine, Durham, North Carolina"},{"name":"Duke University Medical Center, Durham, North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth J.","family":"Lydon","sequence":"additional","affiliation":[{"name":"Duke Clinical Research Institute, Division of Cardiology, Duke University School of Medicine, Durham, North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan P.","family":"Piccini","sequence":"additional","affiliation":[{"name":"Duke Clinical Research Institute, Division of Cardiology, Duke University School of Medicine, Durham, North Carolina"},{"name":"Duke University Medical Center, Durham, North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Viethen","sequence":"additional","affiliation":[{"name":"Bayer AG, Wuppertal, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonas","family":"Oldgren","sequence":"additional","affiliation":[{"name":"Uppsala Clinical Research Center, Department of Medical Sciences, Uppsala University, Uppsala, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaun G.","family":"Goodman","sequence":"additional","affiliation":[{"name":"Canadian VIGOUR Centre, University of Alberta, Edmonton, Canada"},{"name":"St Michael\u2019s Hospital, Unity Health Toronto, Peter Munk Cardiac Centre, University Health Network, University of Toronto, Toronto, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Steffel","sequence":"additional","affiliation":[{"name":"Hirslanden Clinic Zurich, Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea M.","family":"Russo","sequence":"additional","affiliation":[{"name":"Cooper Medical School of Rowan University, Camden, New Jersey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabelle C.","family":"van Gelder","sequence":"additional","affiliation":[{"name":"University of Groningen, University Medical Center, Groningen, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keith C.","family":"Ferdinand","sequence":"additional","affiliation":[{"name":"School of Medicine, Tulane University, New Orleans, Louisiana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renato D.","family":"Lopes","sequence":"additional","affiliation":[{"name":"Duke Clinical Research Institute, Division of Cardiology, Duke University School of Medicine, Durham, North Carolina"},{"name":"Duke University Medical Center, Durham, North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hardi","family":"Mundl","sequence":"additional","affiliation":[{"name":"Bayer AG, Wuppertal, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bela","family":"Benczur","sequence":"additional","affiliation":[{"name":"1st Department of Internal Medicine (Cardiology\/Nephrology), Balassa J\u00e1nos Hospital, Szeksz\u00e1rd, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan Jos\u00e9","family":"G\u00f3mez-Doblas","sequence":"additional","affiliation":[{"name":"\u00c1rea del Coraz\u00f3n, Hospital Universitario Virgen de La Victoria, and Instituto de Investigaci\u00f3n Biom\u00e9dica de M\u00e1laga y Plataforma en Nanomedicina, and Departamento de Medicina y Dermatolog\u00eda, Facultad de Medicina, Universidad de M\u00e1laga, M\u00e1laga, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Cardiovasculares, Instituto de Salud Carlos III, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Glikson","sequence":"additional","affiliation":[{"name":"Shaare Zedek Medical Center, Jerusalem, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Assen","family":"Goudev","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Queen Giovanna University Hospital, Medical University of Sofia, Sofia, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erik L.","family":"Grove","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Aarhus University Hospital, and Department of Clinical Medicine, Faculty of Health, Aarhus University, Aarhus, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sigrun","family":"Halvorsen","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Oslo University Hospital Ullev\u00e5l, Oslo, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tuomas","family":"Kiviniemi","sequence":"additional","affiliation":[{"name":"Heart Center, Turku University Hospital, University of Turku, Turku, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne-C\u00e9line","family":"Martin","sequence":"additional","affiliation":[{"name":"Cardiology Department, European Hospital Georges Pompidou, Assistance Publique H\u00f4pitaux de Paris, Centre-Universit\u00e9 Paris Cit\u00e9, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roopinder K.","family":"Sandhu","sequence":"additional","affiliation":[{"name":"Canadian VIGOUR Centre, University of Alberta, Edmonton, Alberta, Canada"},{"name":"Libin Cardiovascular Institute, University of Calgary, Calgary, Alberta, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dragos","family":"Vinereanu","sequence":"additional","affiliation":[{"name":"University of Medicine and Pharmacy Carol Davila, Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank W.","family":"Rockhold","sequence":"additional","affiliation":[{"name":"Duke Clinical Research Institute, Division of Cardiology, Duke University School of Medicine, Durham, North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valeria","family":"Caso","sequence":"additional","affiliation":[{"name":"University of Perugia Stroke Unit, Perugia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosa","family":"Coppolecchia","sequence":"additional","affiliation":[{"name":"Bayer US LLC, Whippany, New Jersey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manesh R.","family":"Patel","sequence":"additional","affiliation":[{"name":"Duke Clinical Research Institute, Division of Cardiology, Duke University School of Medicine, Durham, North Carolina"},{"name":"Duke University Medical Center, Durham, North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"10","reference":[{"issue":"4","key":"hoi250006r1","doi-asserted-by":"publisher","first-page":"242","DOI":"10.1161\/CIRCULATIONAHA.121.056355","article-title":"Direct oral anticoagulants vs warfarin in patients with atrial fibrillation: patient-level network meta-analyses of randomized clinical trials with interaction testing by age and 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