{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T13:53:01Z","timestamp":1791553981620,"version":"4.3.4"},"reference-count":111,"publisher":"American Chemical Society (ACS)","issue":"10","license":[{"start":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T00:00:00Z","timestamp":1789084800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000057","name":"U.S. Department of Health and Human Services","doi-asserted-by":"publisher","award":["R16GM149412"],"award-info":[{"award-number":["R16GM149412"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,10,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Ischemic stroke remains a leading contributor to global mortality and long-term disability, while bleeding complications, particularly intracranial hemorrhage, continue to constrain the use of conventional antithrombotic therapies for secondary prevention. Factor XI (FXI) has emerged as an attractive therapeutic target because it promotes thrombin amplification and pathological thrombus stabilization while contributing only modestly to physiological hemostasis, forming the basis for \u201chemostasis-sparing\u201d anticoagulation. Current FXI-targeted approaches include oral small-molecule FXIa inhibitors (asundexian and milvexian), antisense oligonucleotides (fesomersen), and monoclonal antibodies (abelacimab and osocimab). Among these, oral FXIa inhibitors appear particularly suited for long-term cerebrovascular prevention because they provide rapid, reversible target inhibition. Phase II trials, including PACIFIC-Stroke and AXIOMATIC-SSP, showed neutral primary efficacy end points but consistently favorable safety outcomes. More recently, the phase III OCEANIC-STROKE trial demonstrated that asundexian 50 mg once daily added to antiplatelet therapy reduced recurrent ischemic stroke by 26% (HR 0.74; 95% CI 0.65\u20130.84) without a significant increase in major bleeding among patients with noncardioembolic stroke. In contrast, OCEANIC-AF showed inferior efficacy compared with apixaban in atrial fibrillation, suggesting that the therapeutic value of FXIa inhibition is strongly dependent on clinical context. Taken together, this review summarizes the pathophysiological rationale, pharmacology, and clinical evidence supporting FXI inhibition for secondary ischemic stroke prevention and discusses future precision-medicine strategies for patient selection.<\/jats:p>","DOI":"10.1021\/acsptsci.6c00298","type":"journal-article","created":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T15:01:47Z","timestamp":1789138907000},"page":"2675-2687","source":"Crossref","is-referenced-by-count":0,"title":["Factor XI(a) Inhibition\nin Secondary Stroke Prevention:\nOn the Cusp of a New Anticoagulation Paradigm"],"prefix":"10.1021","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9146-2662","authenticated-orcid":true,"given":"Rami A.","family":"Al-Horani","sequence":"first","affiliation":[{"name":"Xavier University of Louisiana , , ,","place":["New Orleans, Louisiana, United States, 70125"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,9,11]]},"reference":[{"issue":"10","key":"2026100909095607800_cit1","doi-asserted-by":"publisher","first-page":"973","DOI":"10.1016\/S1474-4422(24)00369-7","article-title":"Global, regional, and national burden of stroke and\nits risk factors, 1990\u20132021: a systematic analysis for the\nGlobal Burden of Disease Study 2021","volume":"23","author":"GBD 2021 Stroke Risk Factor Collaborators.","year":"2024","journal-title":"Lancet\nNeurol."},{"issue":"8","key":"2026100909095607800_cit2","doi-asserted-by":"publisher","first-page":"784","DOI":"10.1056\/NEJMcp2415601","article-title":"Secondary Prevention after Ischemic\nStroke","volume":"394","author":"Furie","year":"2026","journal-title":"N Engl J. 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Thromb Haemost."},{"issue":"8","key":"2026100909095607800_cit31","doi-asserted-by":"publisher","first-page":"3035","DOI":"10.1182\/blood.V86.8.3035.3035","article-title":"Feedback activation\nof factor XI by thrombin in plasma results in additional formation\nof thrombin that protects fibrin clots from fibrinolysis","volume":"86","author":"von dem Borne","year":"1995","journal-title":"Blood"},{"issue":"8","key":"2026100909095607800_cit32","doi-asserted-by":"publisher","first-page":"1603","DOI":"10.1111\/jth.13342","article-title":"Reduced fibrinolytic\nresistance in patients with factor XI deficiency. Evidence of a thrombin-independent\nimpairment of the thrombin-activatable fibrinolysis inhibitor pathway","volume":"14","author":"Colucci","year":"2016","journal-title":"J. Thromb Haemost."},{"issue":"1","key":"2026100909095607800_cit33","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1172\/JCI781","article-title":"Enhancement\nof rabbit jugular vein\nthrombolysis by neutralization of factor XI. In vivo evidence for\na role of factor XI as an anti-fibrinolytic factor","volume":"101","author":"Minnema","year":"1998","journal-title":"J. Clin Invest."},{"issue":"1","key":"2026100909095607800_cit34","doi-asserted-by":"publisher","first-page":"9761","DOI":"10.1038\/s41598-022-13174-5","article-title":"Association of FXI\nactivity with thrombo-inflammation, extracellular matrix, lipid metabolism\nand apoptosis in venous thrombosis","volume":"12","author":"Pallares Robles","year":"2022","journal-title":"Sci. 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