{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T12:30:41Z","timestamp":1776774641354,"version":"3.51.2"},"reference-count":25,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2026,2,12]],"date-time":"2026-02-12T00:00:00Z","timestamp":1770854400000},"content-version":"vor","delay-in-days":11,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T00:00:00Z","timestamp":1769904000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Cardiology"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Factor XI\/XIa inhibitors are emerging anticoagulants with potential to reduce bleeding complications in atrial fibrillation (AF) patients. This meta\u2010analysis evaluated their efficacy and safety compared to direct oral anticoagulants (DOACs) and explored dose optimization.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A systematic search of PubMed, Cochrane, and Embase was conducted through March 2025 following PRISMA guidelines. Randomized controlled trials (RCTs) comparing Factor XI\/XIa inhibitors with DOACs in AF patients were included. Outcomes assessed were major bleeding, stroke, systemic embolism, all\u2010cause and cardiovascular mortality and serious adverse events. Risk ratios (RR) with 95% confidence intervals (CI) were pooled using a Mantel\u2010Haenszel random\u2010effects model. Heterogeneity was evaluated with the I\u00b2 statistic, and evidence certainty assessed by the GRADE approach. Trial Sequential Analysis (TSA) was performed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Three RCTs including 16,772 patients (mean age 73 years, CHA\u2082DS\u2082\u2010VASc 3.9\u20135) were analyzed. Factor XI\/XIa inhibitors significantly reduced major bleeding (RR: 0.41, 95% CI: 0.36\u20130.46, I\u00b2 = 0%) compared to DOACs. However, stroke risk was increased (RR: 3.42, 95% CI: 2.62\u20134.46), particularly with asundexian 50\u2009mg (RR: 4.02). No significant differences were observed in all\u2010cause mortality (RR: 0.82) or cardiovascular death (RR: 1.05). Systemic embolism risk was higher (RR: 4.26), while serious adverse events were comparable (RR: 0.95). TSA indicated encouraging safety outcomes but highlighted the need for further large\u2010scale studies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Factor XI\/XIa inhibitors lower major bleeding risk in AF patients but increase stroke and systemic embolism rates without impacting mortality.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/clc.70263","type":"journal-article","created":{"date-parts":[[2026,2,12]],"date-time":"2026-02-12T12:48:47Z","timestamp":1770900527000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Dose\u2010Response Efficacy and Safety of Factor XI\/XIa Inhibitors in Atrial Fibrillation; a Systematic Review and Meta\u2010Analysis With Subgroup Exploration and Trial Sequential Validation"],"prefix":"10.1002","volume":"49","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-6023-3992","authenticated-orcid":false,"given":"Muhammad Aqib","family":"Faizan","sequence":"first","affiliation":[{"name":"Gomal Medical College Khyber Medical University Peshawar Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tooba","family":"Rehman","sequence":"additional","affiliation":[{"name":"Gomal Medical College Khyber Medical University Peshawar Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mrunalini","family":"Dandamudi","sequence":"additional","affiliation":[{"name":"Montefiore Einstein Medical Center Bronx New York USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jaivardhan A.","family":"Menon","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine, Department of Medicine Brigham and Women's Hospital Boston Massachusetts USA"},{"name":"Harvard Medical School 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USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-6653-0661","authenticated-orcid":false,"given":"Jibran","family":"Ikram","sequence":"additional","affiliation":[{"name":"Cardiovascular Medicine Department Heart, Vascular and Thoracic Institute, Cleveland Clinic Cleveland Ohio USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Moiuz","family":"Chaudhri","sequence":"additional","affiliation":[{"name":"Hackensack Meridian Ocean University Medical Center Brick New Jersey USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carlos","family":"Espiche","sequence":"additional","affiliation":[{"name":"Montefiore Einstein Medical Center Bronx New York USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Main Muhammad Salman","family":"Aslam","sequence":"additional","affiliation":[{"name":"Department of Pulmonary and Critical Care Medicine University of Michigan Ann Arbor  Michigan 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