Predicting clinically relevant bleeding in new-onset atrial fibrillation patients initiating oral anticoagulant therapy: External validation of the AF-BLEED score
- PMID: 41240461
- DOI: 10.1016/j.thromres.2025.109533
Predicting clinically relevant bleeding in new-onset atrial fibrillation patients initiating oral anticoagulant therapy: External validation of the AF-BLEED score
Abstract
Background: Atrial fibrillation/flutter (AF/AFL) is associated with an increased stroke risk, for which oral anticoagulation (OAC) is often indicated. Bleeding risk assessment is crucial in these patients to mitigate bleeding complications, yet AF guidelines do not recommend the use of any bleeding risk score (e.g., HAS-BLED) due to concerns about predictive accuracy. The AF-adapted VTE-BLEED (AF-BLEED) score was developed to predict major bleeding (MB) post-OAC initiation.
Aims: Evaluate the incidence of clinically relevant bleeding, and externally validate the AF-BLEED score in new-onset AF/AFL patients.
Methods: Patients enrolled in the DUTCH-AF registry, who started OAC at diagnosis were studied. AF-BLEED categorized patients as low-risk (score ≤ 3) or high-risk (score > 3) for bleeding. Outcomes were first (i) MB and (ii) composite MB and clinically relevant non-major bleeding (CRNMB), with death and OAC discontinuation as competing events. Discrimination (cumulative AUC [AUCt]) was evaluated at 180 days and 2 years.
Results: 4647 patients (AF-BLEED low-risk: 94.0 %) were included. Cumulative MB incidences for low- and high-risk patients were 0.58 % (95 %CI 0.34-0.82 %) and 1.65 % (0.04-3.26 %) at 180 days (p 0.04), and 1.82 % (1.39-2.26 %) and 5.07 % (2.26-7.87 %) at 2 years (p < 0.001), respectively. Cumulative CRNMB/MB incidences for low- and high-risk patients were 1.81 % (1.39-2.24 %) and 4.13 % (1.62-6.65 %) at 180 days (p 0.01), and 6.37 % (5.58-7.16 %) and 9.68 % (5.91-13.45 %) at 2 years (p 0.04), respectively. Discrimination was poor to moderate for both outcomes at both time windows, ranging between 0.51 and 0.62.
Conclusion: Although AF-BLEED was associated with subsequent risk of clinically relevant bleeding, its discriminative ability was poor, limiting the practical utility in its current form.
Keywords: Anticoagulants; Atrial fibrillation; Clinical decision rules; Hemorrhage; Validation study.
Copyright © 2025 The Authors. Published by Elsevier Ltd.. All rights reserved.
Conflict of interest statement
Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: M.V. Huisman and M.E.W. Hemels reports financial support was provided by Research grant from The Netherlands Organisation for Health Research and Development (ZonMw). M.E.W. Hemels reports financial support was provided by Research grant from Federation of Dutch Thrombosis Services. J. Seelig reports an unrestricted research grant from Federation of Dutch Thrombosis Services, related to this work. L. Voorhout reports a speaker fee from BMS, unrelated to this work. T.A.C. de Vries reports a research grant from The Netherlands Organisation for Health Research and Development (ZonMW), related to this work and paid to his institution. He also reports support for attending meetings and/or travel from Daiichi Sankyo, statistical and editorial support from Daiichi Sankyo, and speaker fees from both Bristol-Myers-Squibb and independent speakers bureaus (Two Hand Events and Mark Two Academy), all unrelated to this work. He also reports to be a member of the adjudication committee of the Low International Normalized Ratio to Minimize Bleeding with Mechanical Valves (LIMIT), The Direct Oral Anticoagulation versus Warfarin after Cardiac Surgery (DANCE) and Apixaban for Stroke Prevention in Subclinical Atrial Fibrillation (ARTERSiA) trials. L.V.A. Boersma reports consultancy fees from Medtronic and Boston Scientific, and speaker fees from Medtronic, Boston Scientific, ZOLL, Abbott, and Johnson&Johnson, outside the submitted work and paid to his institution. H. ten Cate reports consultancy fees from Astra Zeneca, Galapagos, Novostia, Alveron, all unrelated to the present work and paid to his institution, and reports to be a shareholder in Coagulation Profile (no revenues yet). J.R. de Groot is supported by grants from Information Technology for European Advancement-ITEA4 grant number 21026; by CVON/Dutch Heart Foundation grant 01-002-2022-0118 EmbRACE, outside the submitted work. He also received research grant through his institution from Atricure, Bayer, Boston Scientific Daiichi Sankyo, Johnson&Jonson, Medtronic, Philips; and speaker/consultancy fees from Atricure, Bayer, berlin Chemie, Daiichi Sankyo, Johnson&Johnson, Menarini, Novartis, Servier, all unrelated to this work. J.S.S.G. de Jong reports consultancy fees from Medtronic and payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Medtronic, unrelated to the present work. He also reports leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid, as a NHRA board member. F.A. Klok reports unrestricted research funding from Bayer, BMS, BSCI, AstraZeneca, MSD, Leo Pharma, Actelion, Farm-X, angiodynamics, The Netherlands Organisation for Health Research and Development, The Dutch Thrombosis Foundation, The Dutch Heart Foundation and the Horizon Europe Program, all unrelated to this work and paid to his institution. M.J.H.A. Kruip reports speakers fees from Sobi and Roche, paid to the institution, and research grants from Sobi, The Netherlands Organisation for Health Research and Development, The Dutch Thrombosis Association, and the Horizon Europe Program, all unrelated to this work and paid to the institute. She also reports leadership or fiduciary role in other board, society, committee or advocacy group, unpaid, as President of the board of the Federation of Dutch Thrombosis Services (until Oct 2024), and as a board member of the Dutch society of thrombosis and hemostasis. J.G. Luermans reports research grants from The Netherlands Organisation for Health Research and Development (ZonMw) and Medtronic for the LEAP trial (NCT04595487), unrelated to the present work and paid to his institution. He also reports consultancy agreement with Medtronic, paid to the institution, and leadership or fiduciary role in other board, society, committee or advocacy group, unpaid, as Chair of Ablation committee of Netherlands Heart Rhythm Registration. J.G. Meeder reports leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid, as president of The Netherlands Society of Cardiology. T.J. Römer reports serving on advisory boards for AMGEN, Novo Nordisk and Amarin. F. Smeets reports payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from AstraZeneca, and participation on a Data Safety Monitoring Board or Advisory Board for AMGEN. G.J.M. Tahapary reports support for attending and/or travel to the Annual Biosense AF meeting, and he reports to have stocks which do not interfere with his medical profession. R.G. Tieleman reports grants from Medtronic and Abbott, and personal fees from Boehringer Ingelheim, Bayer and Pfizer/Bristol Myers Squibb, all outside submitted work. Additionally, he is coinventor of the MyDiagnostick. S.A.J. Timmer reports to serve as a consultant for Medtronic. S.A. Trines reports consultancy fees from Abbot and payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Biosense Webster, unrelated to this work and paid to his institution. He also reports leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid, as Chair EHRA Core Curriculum writing committee and member of the supervisory board of The Netherlands Society for Cardiology. E.A. de Vrey reports payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events, unrelated to this work, and leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid, as a WCN congress committee member. M.E.W. Hemels reports a research grant from The Netherlands Organisation for Health Research and Development (ZonMw, project numbers 848050006 and 848050007) and a research grant from Federation of Dutch Thrombosis Services, both related to this work. He also reports consultancy/speaker fees from BMS/Pfizer, Daiichi Sankyo, Bayer, Boehringer Ingelheim and Roche diagnostics, all unrelated to this work. M.V. Huisman reports a research grant from The Netherlands Organisation for Health Research and Development (ZonMw, 848050006 and 848050007) related to this work. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
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