Comparative clinical outcomes of acenocoumarol versus direct oral anticoagulants (DOACs) and warfarin in patients with atrial fibrillation: real-world-evidence (SIESTA-A study)

ObjectiveThe 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.MethodsThis was a ret...

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Main Authors: Ma Carmen Montero-Balosa, Juan A. Limón-Mora, Ana Leal-Atienza, Beatriz García-Robredo, Pablo Sánchez-Villegas, Rebeca Isabel-Gómez, Ma José Aguado-Romeo, Luis Gabriel Luque Romero, Ma Teresa Molina-López
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-08-01
Series:Frontiers in Pharmacology
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Online Access:https://www.frontiersin.org/articles/10.3389/fphar.2025.1548298/full
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author Ma Carmen Montero-Balosa
Juan A. Limón-Mora
Ana Leal-Atienza
Beatriz García-Robredo
Pablo Sánchez-Villegas
Rebeca Isabel-Gómez
Ma José Aguado-Romeo
Luis Gabriel Luque Romero
Ma Teresa Molina-López
author_facet Ma Carmen Montero-Balosa
Juan A. Limón-Mora
Ana Leal-Atienza
Beatriz García-Robredo
Pablo Sánchez-Villegas
Rebeca Isabel-Gómez
Ma José Aguado-Romeo
Luis Gabriel Luque Romero
Ma Teresa Molina-López
author_sort Ma Carmen Montero-Balosa
collection DOAJ
description ObjectiveThe 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.MethodsThis 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.ResultsA 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 0.93–1.22); dabigatran (RR:1.17; 95%CI 1.02–1.33); rivaroxaban (RR:1.15; 95%CI 1.05–1.26); apixaban (RR: 0.96; 95%CI 0.87–1.07) and edoxaban (RR: 1.10; 95%CI 0.79–1.51). Compared to acenocoumarol, the risk of all-cause mortality was lower for dabigatran, rivaroxaban and apixaban (RR:0.77; 95%CI 0.72–0.82; RR:0.79; 95%CI 0.76–0.83; RR:0.85; 95%CI 0.81–0.89, respectively) and higher for warfarin (RR:1.12; 95%CI 1.05–1.20). An increased risk of gastrointestinal bleeding was observed with dabigatran (RR:1.36; 95%CI 1.09–1.70) and a lower risk with rivaroxaban (RR:0.84; 95%CI 0.72–0.98). 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 1.31–2.06) and intracranial bleeding (RR:1.61; 95%CI 1.22–2.13) 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.ConclusionAlthough 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.
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spelling doaj-art-c3e6101bfa9d4c69b5fac677218455482025-08-20T03:58:11ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122025-08-011610.3389/fphar.2025.15482981548298Comparative clinical outcomes of acenocoumarol versus direct oral anticoagulants (DOACs) and warfarin in patients with atrial fibrillation: real-world-evidence (SIESTA-A study)Ma Carmen Montero-Balosa0Juan A. Limón-Mora1Ana Leal-Atienza2Beatriz García-Robredo3Pablo Sánchez-Villegas4Rebeca Isabel-Gómez5Ma José Aguado-Romeo6Luis Gabriel Luque Romero7Ma Teresa Molina-López8Primary Care Pharmacy, Aljarafe-Sevilla Norte District. Andalusian Health Service, Seville, SpainCoordination of Management and Evaluation, Andalusian Health Service., Seville, SpainAndalusian Public Foundation for the Management of Health Research in Seville (FISEVI), Seville, SpainPrimary Care Pharmacy, Seville District. Andalusian Health Service, Seville, SpainAndalusian School of Public Health, Granada, SpainAndalusian Health Technology Assessment Area, Progress and Health Foundation, Seville, SpainCenter for the Transfusion of Tissues and Cells, Seville, SpainResearch Unit, Andalusian Health Service, Seville, SpainPrimary Care Pharmacy, Seville District. Andalusian Health Service, Seville, SpainObjectiveThe 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.MethodsThis 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.ResultsA 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 0.93–1.22); dabigatran (RR:1.17; 95%CI 1.02–1.33); rivaroxaban (RR:1.15; 95%CI 1.05–1.26); apixaban (RR: 0.96; 95%CI 0.87–1.07) and edoxaban (RR: 1.10; 95%CI 0.79–1.51). Compared to acenocoumarol, the risk of all-cause mortality was lower for dabigatran, rivaroxaban and apixaban (RR:0.77; 95%CI 0.72–0.82; RR:0.79; 95%CI 0.76–0.83; RR:0.85; 95%CI 0.81–0.89, respectively) and higher for warfarin (RR:1.12; 95%CI 1.05–1.20). An increased risk of gastrointestinal bleeding was observed with dabigatran (RR:1.36; 95%CI 1.09–1.70) and a lower risk with rivaroxaban (RR:0.84; 95%CI 0.72–0.98). 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 1.31–2.06) and intracranial bleeding (RR:1.61; 95%CI 1.22–2.13) 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.ConclusionAlthough 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.https://www.frontiersin.org/articles/10.3389/fphar.2025.1548298/fulloral anticoagulant agentsoral direct anticoagulantssafetyhealth outcomeseffectiveness
spellingShingle Ma Carmen Montero-Balosa
Juan A. Limón-Mora
Ana Leal-Atienza
Beatriz García-Robredo
Pablo Sánchez-Villegas
Rebeca Isabel-Gómez
Ma José Aguado-Romeo
Luis Gabriel Luque Romero
Ma Teresa Molina-López
Comparative clinical outcomes of acenocoumarol versus direct oral anticoagulants (DOACs) and warfarin in patients with atrial fibrillation: real-world-evidence (SIESTA-A study)
Frontiers in Pharmacology
oral anticoagulant agents
oral direct anticoagulants
safety
health outcomes
effectiveness
title Comparative clinical outcomes of acenocoumarol versus direct oral anticoagulants (DOACs) and warfarin in patients with atrial fibrillation: real-world-evidence (SIESTA-A study)
title_full Comparative clinical outcomes of acenocoumarol versus direct oral anticoagulants (DOACs) and warfarin in patients with atrial fibrillation: real-world-evidence (SIESTA-A study)
title_fullStr Comparative clinical outcomes of acenocoumarol versus direct oral anticoagulants (DOACs) and warfarin in patients with atrial fibrillation: real-world-evidence (SIESTA-A study)
title_full_unstemmed Comparative clinical outcomes of acenocoumarol versus direct oral anticoagulants (DOACs) and warfarin in patients with atrial fibrillation: real-world-evidence (SIESTA-A study)
title_short Comparative clinical outcomes of acenocoumarol versus direct oral anticoagulants (DOACs) and warfarin in patients with atrial fibrillation: real-world-evidence (SIESTA-A study)
title_sort comparative clinical outcomes of acenocoumarol versus direct oral anticoagulants doacs and warfarin in patients with atrial fibrillation real world evidence siesta a study
topic oral anticoagulant agents
oral direct anticoagulants
safety
health outcomes
effectiveness
url https://www.frontiersin.org/articles/10.3389/fphar.2025.1548298/full
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