{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,18]],"date-time":"2026-04-18T01:04:22Z","timestamp":1776474262162,"version":"3.51.2"},"reference-count":41,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,8,1]],"date-time":"2025-08-01T00:00:00Z","timestamp":1754006400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010154","name":"Fundaci\u00f3n P\u00fablica Andaluza para La Gesti\u00f3n de la Investigaci\u00f3n en Salud de Sevilla","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010154","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>The aim of this study was to evaluate the effectiveness and safety of direct oral anticoagulants (DOACs: dabigatran, rivaroxaban, apixaban and edoxaban) and warfarin versus acenocoumarol in patients with atrial fibrillation under real-world clinical practice conditions.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This was a retrospective, real-world data-based study. The data source was the Andalusian Population Health Database. The study covered the period from January 2012 to December 2020. Effectiveness outcomes were defined as the identification of a first occurrence of ischaemic or bleeding events, or all-cause mortality. The statistical analysis included crude incidence analysis, survival models: Kaplan-Meier curves, propensity score matched pairs analysis, Fine-Gray model, and Cox regression analysis adjusted for possible confounding.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A total of 150,949 patients were included. The mean age of the cohort was 74 years (48.2% female). The mean follow-up time was 3.3 years. The combined effectiveness endpoint of ischaemic events (transient ischaemic attack, systemic embolism, pulmonary embolism, or ischaemic stroke) showed the following results compared to acenocoumarol: warfarin (RR:1.06; 95%CI 0.93\u20131.22); dabigatran (RR:1.17; 95%CI 1.02\u20131.33); rivaroxaban (RR:1.15; 95%CI 1.05\u20131.26); apixaban (RR: 0.96; 95%CI 0.87\u20131.07) and edoxaban (RR: 1.10; 95%CI 0.79\u20131.51). Compared to acenocoumarol, the risk of all-cause mortality was lower for dabigatran, rivaroxaban and apixaban (RR:0.77; 95%CI 0.72\u20130.82; RR:0.79; 95%CI 0.76\u20130.83; RR:0.85; 95%CI 0.81\u20130.89, respectively) and higher for warfarin (RR:1.12; 95%CI 1.05\u20131.20). An increased risk of gastrointestinal bleeding was observed with dabigatran (RR:1.36; 95%CI 1.09\u20131.70) and a lower risk with rivaroxaban (RR:0.84; 95%CI 0.72\u20130.98). All 4 DOACs showed a lower risk of intracranial bleeding compared to acenocoumarol. Warfarin carried a higher risk of both gastrointestinal bleeding (RR:1.64; 95%CI 1.31\u20132.06) and intracranial bleeding (RR:1.61; 95%CI 1.22\u20132.13) compared to acenocoumarol. An unadjusted analysis of matched groups in a multivariate Cox regression analysis yielded similar results for combined effectiveness and safety outcomes compared to acenocoumarol.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Although DOACs were clearly associated with a lower risk of intracranial bleeding compared to acenocoumarol, our data did not reveal a significant reduction in thromboembolic events. Warfarin was found to be both less effective and less safe than acenocoumarol.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fphar.2025.1548298","type":"journal-article","created":{"date-parts":[[2025,8,1]],"date-time":"2025-08-01T05:32:36Z","timestamp":1754026356000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Comparative clinical outcomes of acenocoumarol versus direct oral anticoagulants (DOACs) and warfarin in patients with atrial fibrillation: real-world-evidence (SIESTA-A study)"],"prefix":"10.3389","volume":"16","author":[{"given":"Ma Carmen","family":"Montero-Balosa","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juan A.","family":"Lim\u00f3n-Mora","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ana","family":"Leal-Atienza","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Beatriz","family":"Garc\u00eda-Robredo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pablo","family":"S\u00e1nchez-Villegas","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rebeca","family":"Isabel-G\u00f3mez","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ma Jos\u00e9","family":"Aguado-Romeo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luis Gabriel","family":"Luque Romero","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ma Teresa","family":"Molina-L\u00f3pez","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2025,8,1]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1016\/j.rec.2019.02.021","article-title":"Direct oral anticoagulants versus vitamin K antagonists in real-world patients with nonvalvular atrial fibrillation. 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