{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T17:54:49Z","timestamp":1792691689881,"version":"4.5.0"},"reference-count":18,"publisher":"SAGE Publications","issue":"7","license":[{"start":{"date-parts":[[2026,4,26]],"date-time":"2026-04-26T00:00:00Z","timestamp":1777161600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,4,26]],"date-time":"2026-04-26T00:00:00Z","timestamp":1777161600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"DOI":"10.13039\/501100000274","name":"British Heart Foundation","doi-asserted-by":"publisher","award":["CS\/17\/6\/33361"],"award-info":[{"award-number":["CS\/17\/6\/33361"]}],"id":[{"id":"10.13039\/501100000274","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["International Journal of Stroke"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Randomized trials have demonstrated that early anticoagulation after acute atrial fibrillation-associated ischemic stroke is safe and non-inferior to delayed initiation. Whether anticoagulation should be delayed in people with larger infarcts is uncertain.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Aims:<\/jats:title>\n                    <jats:p>To investigate whether ischemic stroke infarct volume, measured precisely by segmentation, modifies the treatment effect of early anticoagulation with a direct oral anticoagulant (DOAC).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>We did a prespecified secondary analysis of OPTIMAS (NCT: 03759938), a randomized, parallel-group, open-label trial with blinded outcome assessment which randomized people with acute ischemic stroke and atrial fibrillation to early initiation of any licensed DOAC, within 4\u2009days of onset, or delayed initiation 7\u201314\u2009days from onset. The primary outcome was a composite of recurrent ischemic stroke, symptomatic intracranial hemorrhage (ICH), and systemic arterial embolism within 90\u2009days. A central neuroimaging laboratory determined infarct volume using diffusion-weighted magnetic resonance imaging (MRI) using a validated deep learning segmentation model; on computed tomography (CT), infarcts were segmented manually. We modeled infarct volume as a continuous variable using restricted cubic splines and tested for an interaction with treatment allocation in mixed effects logistic regression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      We included 3572 participants (mean age\u2009=\u200978\u2009\u00b1\u200910\u2009years, 45% female), 98.6% of the main trial population. The effect of early versus delayed anticoagulation did not vary with infarct volume (p\n                      <jats:sub>interaction<\/jats:sub>\n                      \u2009=\u20090.18). Rates of the primary outcome were 17\/568 (3.0%) and 12\/599 (2.0%) for early versus delayed initiation with infarcts of 0\u20135\u2009mL; 6\/220 (2.7%) and 11\/229 (4.8%) with infarcts of 5\u201310\u2009mL; 13\/258 (4.6%) and 10\/283 (3.5%) with infarcts of 10\u201325\u2009mL; 6\/145 (4.1%) and 8\/145 (5.5%) with infarcts of 25\u201350\u2009mL; 1\/93 (1.1%) and 7\/94 (7.4%) with infarcts of &gt;50\u2009mL; and 14\/481 (2.9%) and 10\/430 (2.2%) in participants with no infarct visible on clinically acquired brain imaging. Corresponding odds ratios and 95% confidence intervals were 1.52 (0.71\u20133.20), 0.55 (0.20\u20131.51), 1.29 (0.55\u20133.00), 0.74 (0.25\u20132.21), 0.13 (0.02\u20131.11), and 1.25 (0.55\u20132.86), respectively. There were no increased rates of symptomatic ICH with respect to anticoagulation timing for those with large infarcts (&gt;25\u2009mL); there were 3\/238 (1.3%) events in the early group and 5\/239 (2.1%) in the delayed group.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>The treatment effect of early anticoagulation with a DOAC in acute ischemic stroke associated with atrial fibrillation was not modified by infarct volume. Adverse outcomes were not increased with early anticoagulation in people with larger infarcts. Our results provide no evidence that anticoagulation initiation should be delayed beyond 4\u2009days on the basis of infarct size.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/17474930261441297","type":"journal-article","created":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T09:12:13Z","timestamp":1774861933000},"page":"956-967","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":3,"title":["Early versus delayed anticoagulation in acute ischemic stroke with atrial fibrillation according to infarct volume and location: A prespecified subgroup analysis of the OPTIMAS randomized controlled trial"],"prefix":"10.1177","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2428-1575","authenticated-orcid":false,"given":"Philip S","family":"Nash","sequence":"first","affiliation":[{"name":"Stroke Research Centre, Department of Translational Neuroscience and Stroke, UCL Queen Square Institute of Neurology, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4243-5753","authenticated-orcid":false,"given":"Jonathan G","family":"Best","sequence":"additional","affiliation":[{"name":"Stroke Research Centre, Department of Translational Neuroscience and Stroke, UCL Queen Square Institute of Neurology, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Lyon","sequence":"additional","affiliation":[{"name":"Stroke Research Centre, Department of Translational Neuroscience and Stroke, UCL Queen Square Institute of Neurology, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James K","family":"Ruffle","sequence":"additional","affiliation":[{"name":"High Dimensional Neurology Group, Department of Translational Neuroscience and Stroke, UCL Queen Square Institute of Neurology, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8673-7040","authenticated-orcid":false,"given":"Thanyalak","family":"Amornpojnimman","sequence":"additional","affiliation":[{"name":"Stroke Research Centre, Department of Translational Neuroscience and Stroke, UCL Queen Square Institute of Neurology, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rom","family":"Mendel","sequence":"additional","affiliation":[{"name":"Stroke Research Centre, Department of Translational Neuroscience and Stroke, UCL Queen Square Institute of Neurology, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chris","family":"Foulon","sequence":"additional","affiliation":[{"name":"High Dimensional Neurology Group, Department of Translational Neuroscience and Stroke, UCL Queen Square Institute of Neurology, London, UK"},{"name":"Groupe d\u2019Imagerie Neurofonctionnelle (GIN), Institut des Maladies Neurodegeneratives-UMR, CNRS, Bordeaux, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hakim-Moulay","family":"Dehbi","sequence":"additional","affiliation":[{"name":"Comprehensive Clinical Trials Unit, Institute of Clinical Trials and Methodology, UCL, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norin","family":"Ahmed","sequence":"additional","affiliation":[{"name":"Comprehensive Clinical Trials Unit, Institute of Clinical Trials and Methodology, UCL, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liz","family":"Arram","sequence":"additional","affiliation":[{"name":"Stroke Research Centre, Department of Translational Neuroscience and Stroke, UCL Queen Square Institute of Neurology, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maryam","family":"Balogun","sequence":"additional","affiliation":[{"name":"Comprehensive Clinical Trials Unit, Institute of Clinical Trials and 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