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We conducted a PRISMA\u2010guided systematic review and meta\u2010analysis of studies comparing LAAC with medical therapy in AF adults. PubMed, Embase, Scopus, ClinicalTrial. gov, and Cochrane Library were searched from inception to March 2026. Outcomes included all\u2010cause mortality, any stroke, ischemic stroke, hemorrhagic stroke, major bleeding, systemic embolism and cardiac death. Risk ratios (RRs) with 95% confidence intervals (CIs) were pooled using random\u2010effects models. Reconstructed individual patient\u2010level survival data from published Kaplan\u2013Meier curves were used for time\u2010to\u2010event analyses. Trial sequential analysis (TSA) assessed the conclusiveness of cumulative evidence. Six randomized controlled trials involving 7004 patients were included. LAAC demonstrated comparable outcomes to medical therapy for all\u2010cause mortality, any stroke, major bleeding, systemic embolism, and cardiac death. There was a non\u2010significant trend toward increased ischemic stroke and reduced hemorrhagic stroke with LAAC. Reconstructed time\u2010to\u2010event analyses showed similar cumulative incidence of stroke and bleeding outcomes over follow\u2010up. TSA demonstrated that the required information size was not reached for any major endpoint, indicating that current evidence remains underpowered and additional randomized trials are needed. LAAC provides similar overall efficacy and safety compared with medical therapy for stroke prevention in AF but should currently remain reserved for selected patients rather than replacing oral anticoagulation broadly. Further adequately powered trials with longer follow\u2010up are required.<\/jats:p>","DOI":"10.1111\/jce.70486","type":"journal-article","created":{"date-parts":[[2026,8,30]],"date-time":"2026-08-30T18:08:02Z","timestamp":1788113282000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["\u201cLeft Atrial Appendage Closure Versus Medical Therapy in Atrial Fibrillation: A Systematic Review and Meta\u2010Analysis of Randomized Controlled Trials\u201d"],"prefix":"10.1111","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-8308-6799","authenticated-orcid":false,"given":"Ali Alsajad Hussein","family":"Al\u2010Janabi","sequence":"first","affiliation":[{"name":"Department of Internal Medicine ALkindy college of medicine\/University of Baghdad Baghdad Iraq"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4298-5456","authenticated-orcid":false,"given":"Ali Saad","family":"Al\u2010Shammari","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, College of Medicine University of Baghdad Baghdad Iraq"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-0933-0426","authenticated-orcid":false,"given":"Ahmed W.","family":"Hageen","sequence":"additional","affiliation":[{"name":"Faculty of Medicine Tanta University Tanta Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdullah Zeyad Hameed","family":"Al\u2010Tuaama","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Privolzhsky Research Medical University Nizhny Novgorod Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-8575-0119","authenticated-orcid":false,"given":"Abdullah Muataz Taha","family":"Al\u2010Ibraheem","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine ALkindy college of medicine\/University of Baghdad Baghdad Iraq"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammad","family":"Shahzaib","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine King Edward Medical University Lahore Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-0125-5801","authenticated-orcid":false,"given":"Diya","family":"Rathi","sequence":"additional","affiliation":[{"name":"Dow University of Health Sciences Karachi Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khadeeja Ali","family":"Hamzah","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine ALkindy college of medicine\/University of Baghdad Baghdad Iraq"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-2832-6270","authenticated-orcid":false,"given":"Mohammedsadeq A.","family":"shweliya","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, College of Medicine University of Baghdad Baghdad Iraq"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yousif Hameed","family":"Kurmasha","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, College of Medicine University of Kufa Najaf Iraq"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-0891-3561","authenticated-orcid":false,"given":"Mohamed","family":"Wagdy","sequence":"additional","affiliation":[{"name":"Faculty of Medicine Modern University for Technology and Information Cairo Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marwan M.","family":"Refaat","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Internal Medicine American University of Beirut Medical Center Beirut Lebanon"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,30]]},"reference":[{"key":"e_1_2_14_2_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm15072641"},{"key":"e_1_2_14_3_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2026.1730240"},{"key":"e_1_2_14_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jscai.2025.104042"},{"key":"e_1_2_14_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijcha.2020.100688"},{"key":"e_1_2_14_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijcha.2026.101907"},{"key":"e_1_2_14_7_1","doi-asserted-by":"publisher","DOI":"10.5339\/qmj.2026.10"},{"key":"e_1_2_14_8_1","doi-asserted-by":"publisher","DOI":"10.1177\/10760296261442055"},{"key":"e_1_2_14_9_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm15072626"},{"key":"e_1_2_14_10_1","doi-asserted-by":"crossref","unstructured":"M. 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