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Multiple trials have tested more aggressive strategies using long-term combination antiplatelet medications or full-dose anticoagulation with limited evidence of a reduction in ischemic events but a relatively consistent increased risk of bleeding. Emerging new agents targeting factor XI\/XIa may uncouple necessary hemostasis from pathological thrombosis and offer promise for enhancing secondary prevention of stroke without increasing bleeding. The recently positive OCEANIC-STROKE trial (Oral Factor Eleven A Inhibitor Asundexian as Novel Antithrombotic) testing dual-pathway inhibition with the factor XIa inhibitor asundexian in combination with antiplatelet therapy represents a major advance in antithrombotic therapy for noncardioembolic stroke. This review summarizes the current state of the evidence for antithrombotic therapy in secondary stroke prevention after noncardioembolic stroke and discusses completed and ongoing trials of novel factor XI\/XIa inhibitors for stroke prevention.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/strokeaha.125.054846","type":"journal-article","created":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T09:00:15Z","timestamp":1773392415000},"page":"1439-1449","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":3,"title":["Antithrombotic Therapy for Noncardioembolic Ischemic Stroke: Current Evidence and Future Directions"],"prefix":"10.1161","volume":"57","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5218-9015","authenticated-orcid":true,"given":"Brett","family":"Cucchiara","sequence":"first","affiliation":[{"name":"Department of Neurology, University of Pennsylvania, Philadelphia (B.C.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6445-582X","authenticated-orcid":true,"given":"Jean M.","family":"Connors","sequence":"additional","affiliation":[{"name":"Cancer Hematology Division, Dana Farber Cancer Institute, Boston, MA (J.M.C.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8359-2838","authenticated-orcid":true,"given":"Alejandro A.","family":"Rabinstein","sequence":"additional","affiliation":[{"name":"Department of Neurology, Mayo Clinic, Rochester, MN (A.A.R.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6119-342X","authenticated-orcid":true,"given":"Mukul","family":"Sharma","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Neurology, Population Health Research Institute, Hamilton Health Sciences and McMaster University, Hamilton, ON, Canada (M.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(24)00369-7"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIR.0000000000000757"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jstrokecerebrovasdis.2021.105935"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.122.039438"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.120.029972"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.120.028992"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.123.043630"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.26332"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1802712"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.119.027970"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(16)30506-2"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1161\/STR.0000000000000375"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1177\/23969873221100032"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(09)60503-1"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(97)04011-7"},{"key":"e_1_3_2_17_2","doi-asserted-by":"crossref","first-page":"1641","DOI":"10.1016\/S0140-6736(97)04010-5","article-title":"CAST: randomised placebo-controlled trial of early aspirin use in 20,000 patients with acute ischaemic stroke. 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