{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,20]],"date-time":"2025-11-20T12:34:41Z","timestamp":1763642081104,"version":"3.45.0"},"reference-count":19,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2025,11,20]],"date-time":"2025-11-20T00:00:00Z","timestamp":1763596800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background: Current ESC guidelines recommend the use of oral anticoagulant therapy in patients with atrial fibrillation to reduce the risk of arterial embolization. Recently, Factor XIa inhibitors were investigated as an alternative to the commonly used DOACs. Aims: This systematic review and meta-analysis aim to assess whether Factor XIa inhibitors lead to lower risks of bleeding compared to DOACs in patients with atrial fibrillation. Methods: PubMed, Cochrane, and EMBASE were searched. The primary endpoint was the occurrence of a composite of Major or clinically relevant non-major bleeding. Secondary endpoints included death from any cause, cardiovascular death, any adverse effects, any serious adverse effects, minor bleeding, stroke, or systemic embolism. Results: A total of 3 studies met the inclusion criteria and were included in the qualitative and quantitative analysis, comprising 16,772 patients. Factor XIa inhibitors were associated with significantly fewer major or clinically relevant non-major bleedings than DOACs (RR = 0.40 [95% CI [0.32, 0.51]), I2 = 3%, p &lt; 0.00001). There were no differences between Factor XIa inhibitors and DOACs regarding the occurrence of death (RR = 0.83 [95% CI 0.63, 1.08]), I2 = 0%, (p = 0.15) and cardiovascular death (RR = 1.09 [95% CI 0.74, 1.63]), I2 = 0%, (p = 0.65). Interestingly, the risk of stroke and systemic embolism was higher among the patients exposed to factor XIa inhibitors compared to the DOACs group RR = 6.05 [95% CI [1.02, 35.94]), I2 = 5%, (p = 0.05). Conclusions: Factor XIa inhibitors are superior to DOACs in terms of bleeding complications. However, this meta-analysis shows a significantly higher risk of stroke or systemic embolism as compared to commonly used DOACs.<\/jats:p>","DOI":"10.3390\/jcm14228234","type":"journal-article","created":{"date-parts":[[2025,11,20]],"date-time":"2025-11-20T10:30:59Z","timestamp":1763634659000},"page":"8234","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Balancing Safety and Efficacy: Factor XIa INHIBITORS vs. DOACs in Patients with Atrial Fibrillation: A Systematic Review and Meta-Analysis of Randomized Controlled Trials"],"prefix":"10.3390","volume":"14","author":[{"given":"Jacinthe","family":"Khater","sequence":"first","affiliation":[{"name":"DCB Academy, 20143 Milan, Italy"},{"name":"Faculty of Medical Sciences, Rafic Hariri University Campus, Lebanese University, Hadath 6573, Lebanon"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6543-7567","authenticated-orcid":false,"given":"Marco","family":"Frazzetto","sequence":"additional","affiliation":[{"name":"DCB Academy, 20143 Milan, Italy"},{"name":"Harrington Heart and Vascular Institute, University Hospitals, Cleveland, OH 44106, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7628-7333","authenticated-orcid":false,"given":"Shamin Hayat","family":"Mahmud","sequence":"additional","affiliation":[{"name":"Harrington Heart and Vascular Institute, University Hospitals, Cleveland, OH 44106, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9793-3162","authenticated-orcid":false,"given":"Ashkan","family":"Yahyavi","sequence":"additional","affiliation":[{"name":"Harrington Heart and Vascular Institute, University Hospitals, Cleveland, OH 44106, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-1141-9910","authenticated-orcid":false,"given":"Sara","family":"Malakouti","sequence":"additional","affiliation":[{"name":"DCB Academy, 20143 Milan, Italy"},{"name":"Fondazione Ricerca e Innovazione Cardiovascolare, 20143 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bharat","family":"Khialani","sequence":"additional","affiliation":[{"name":"DCB Academy, 20143 Milan, Italy"},{"name":"Tan Tock Seng Hospital, National Healthcare Group, Singapore 308433, Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5808-7810","authenticated-orcid":false,"given":"Bernardo","family":"Cortese","sequence":"additional","affiliation":[{"name":"DCB Academy, 20143 Milan, Italy"},{"name":"Harrington Heart and Vascular Institute, University Hospitals, Cleveland, OH 44106, USA"},{"name":"Fondazione Ricerca e Innovazione Cardiovascolare, 20143 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"100786","DOI":"10.1016\/j.lanepe.2023.100786","article-title":"Atrial fibrillation: Epidemiology, screening and digital health","volume":"37","author":"Linz","year":"2024","journal-title":"Lancet Reg. 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Heart J."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/14\/22\/8234\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,20]],"date-time":"2025-11-20T12:21:20Z","timestamp":1763641280000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/14\/22\/8234"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,20]]},"references-count":19,"journal-issue":{"issue":"22","published-online":{"date-parts":[[2025,11]]}},"alternative-id":["jcm14228234"],"URL":"https:\/\/doi.org\/10.3390\/jcm14228234","relation":{},"ISSN":["2077-0383"],"issn-type":[{"type":"electronic","value":"2077-0383"}],"subject":[],"published":{"date-parts":[[2025,11,20]]}}}