Predicting clinically relevant bleeding in new-onset atrial fibrillation patients initiating oral anticoagulant therapy: External validation of the AF-BLEED score

S. F. B. van der Horst; G. Chu; J. Seelig; E. M. Trinks-Roerdink; L. Voorhout; T. A. C. de Vries; A. P. van Alem; R. J. Beukema; L. V. A. Boersma; M. A. Brouwer; H. ten Cate; L. M. Faber; J. R. de Groot; Y. L. Gu; F. R. den Hartog; J. S. S. G. de Jong; Y. de Jong; C. J. H. J. Kirchhof; F. S. Kleijwegt; F. A. Klok; M. J. H. A. Kruip; T. Lenderink; J. G. Luermans; J. G. Meeder; A. M. Otten; R. Pisters; L. Pos; F. J. Prins; T. J. Römer; F. Smeets; G. J. M. Tahapary; L. J. H. J. Theunissen; R. G. Tieleman; S. A. J. Timmer; V. Tichelaar; S. A. Trines; P. van der Voort; S. Velthuis; E. A. de Vrey; R. J. Walhout; M. E. W. Hemels; F. H. Rutten; G. J. Geersing; M. V. Huisman

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

S. F. B. van der Horst
, G. Chu
, J. Seelig
, E. M. Trinks-Roerdink
, L. Voorhout
, T. A. C. de Vries
, A. P. van Alem
, R. J. Beukema
, L. V. A. Boersma
, M. A. Brouwer
, H. ten Cate
, L. M. Faber
, J. R. de Groot
, Y. L. Gu
, F. R. den Hartog
, J. S. S. G. de Jong
, Y. de Jong
, C. J. H. J. Kirchhof
, F. S. Kleijwegt
, F. A. Klok

M. J. H. A. Kruip, T. Lenderink, J. G. Luermans, J. G. Meeder, A. M. Otten, R. Pisters, L. Pos, F. J. Prins, T. J. Römer, F. Smeets, G. J. M. Tahapary, L. J. H. J. Theunissen, R. G. Tieleman, S. A. J. Timmer, V. Tichelaar, S. A. Trines, P. van der Voort, S. Velthuis, E. A. de Vrey, R. J. Walhout, M. E. W. Hemels, F. H. Rutten, G. J. Geersing, M. V. Huisman

Leiden University
Rijnstate Hospital
Utrecht University
Haaglanden Medisch Centrum
Radboud University Nijmegen
St. Antonius Ziekenhuis
Maastricht University
Red Cross Hospital
University of Amsterdam
Ziekenhuis Nij Smellinghe, Drachten
Gelderland Valley Hospital
Onze Lieve Vrouwe Gasthuis
Alrijne Hospital Location Leiderdorp
Erasmus University Rotterdam
Zuyderland
VieCuri Medisch Centrum
Gelre Hospitals
Hospital Group Twente
Elkerliek Ziekenhuis
Bernhoven Hospital
Noordwest Hospital Group
Maxima Medical Centre
Martini Ziekenhuis
University of Groningen
Catharina Hospital
Meander Medical Center

Research output: Contribution to journal › Article › Academic › peer-review

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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.

Original language	English
Article number	109533
Pages (from-to)	109533
Number of pages	1
Journal	Thrombosis research
Volume	256
DOIs	https://doi.org/10.1016/j.thromres.2025.109533
Publication status	Published - 1 Dec 2025

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

Anticoagulants
Atrial fibrillation
Clinical decision rules
Hemorrhage
Validation study

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van der Horst, S. F. B., Chu, G., Seelig, J., Trinks-Roerdink, E. M., Voorhout, L., de Vries, T. A. C., van Alem, A. P., Beukema, R. J., Boersma, L. V. A., Brouwer, M. A., ten Cate, H., Faber, L. M., de Groot, J. R., Gu, Y. L., den Hartog, F. R., de Jong, J. S. S. G., de Jong, Y., Kirchhof, C. J. H. J., Kleijwegt, F. S., ... Huisman, M. V. (2025). Predicting clinically relevant bleeding in new-onset atrial fibrillation patients initiating oral anticoagulant therapy: External validation of the AF-BLEED score. Thrombosis research, 256, 109533. Article 109533. https://doi.org/10.1016/j.thromres.2025.109533

@article{0a035ee8d5c44277891b26055550c38d,

title = "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",

author = "\{van der Horst\}, \{S. F. B.\} and G. Chu and J. Seelig and Trinks-Roerdink, \{E. M.\} and L. Voorhout and \{de Vries\}, \{T. A. C.\} and \{van Alem\}, \{A. P.\} and Beukema, \{R. J.\} and Boersma, \{L. V. A.\} and Brouwer, \{M. A.\} and \{ten Cate\}, H. and Faber, \{L. M.\} and \{de Groot\}, \{J. R.\} and Gu, \{Y. L.\} and \{den Hartog\}, \{F. R.\} and \{de Jong\}, \{J. S. S. G.\} and \{de Jong\}, Y. and Kirchhof, \{C. J. H. J.\} and Kleijwegt, \{F. S.\} and Klok, \{F. A.\} and Kruip, \{M. J. H. A.\} and T. Lenderink and Luermans, \{J. G.\} and Meeder, \{J. G.\} and Otten, \{A. M.\} and R. Pisters and L. Pos and Prins, \{F. J.\} and R{\"o}mer, \{T. J.\} and F. Smeets and Tahapary, \{G. J. M.\} and Theunissen, \{L. J. H. J.\} and Tieleman, \{R. G.\} and Timmer, \{S. A. J.\} and V. Tichelaar and Trines, \{S. A.\} and \{van der Voort\}, P. and S. Velthuis and \{de Vrey\}, \{E. A.\} and Walhout, \{R. J.\} and Hemels, \{M. E. W.\} and Rutten, \{F. H.\} and Geersing, \{G. J.\} and Huisman, \{M. V.\}",

note = "Publisher Copyright: {\textcopyright} 2025 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license. http://creativecommons.org/licenses/by/4.0/",

year = "2025",

month = dec,

day = "1",

doi = "10.1016/j.thromres.2025.109533",

language = "English",

volume = "256",

pages = "109533",

journal = "Thrombosis research",

issn = "0049-3848",

publisher = "Elsevier Limited",

}

van der Horst, SFB, Chu, G, Seelig, J, Trinks-Roerdink, EM, Voorhout, L, de Vries, TAC, van Alem, AP, Beukema, RJ, Boersma, LVA, Brouwer, MA, ten Cate, H, Faber, LM, de Groot, JR, Gu, YL, den Hartog, FR, de Jong, JSSG, de Jong, Y, Kirchhof, CJHJ, Kleijwegt, FS, Klok, FA, Kruip, MJHA, Lenderink, T, Luermans, JG, Meeder, JG, Otten, AM, Pisters, R, Pos, L, Prins, FJ, Römer, TJ, Smeets, F, Tahapary, GJM, Theunissen, LJHJ, Tieleman, RG, Timmer, SAJ, Tichelaar, V, Trines, SA, van der Voort, P, Velthuis, S, de Vrey, EA, Walhout, RJ, Hemels, MEW, Rutten, FH, Geersing, GJ & Huisman, MV 2025, 'Predicting clinically relevant bleeding in new-onset atrial fibrillation patients initiating oral anticoagulant therapy: External validation of the AF-BLEED score', Thrombosis research, vol. 256, 109533, pp. 109533. https://doi.org/10.1016/j.thromres.2025.109533

TY - JOUR

T1 - Predicting clinically relevant bleeding in new-onset atrial fibrillation patients initiating oral anticoagulant therapy

T2 - External validation of the AF-BLEED score

AU - van der Horst, S. F. B.

AU - Chu, G.

AU - Seelig, J.

AU - Trinks-Roerdink, E. M.

AU - Voorhout, L.

AU - de Vries, T. A. C.

AU - van Alem, A. P.

AU - Beukema, R. J.

AU - Boersma, L. V. A.

AU - Brouwer, M. A.

AU - ten Cate, H.

AU - Faber, L. M.

AU - de Groot, J. R.

AU - Gu, Y. L.

AU - den Hartog, F. R.

AU - de Jong, J. S. S. G.

AU - de Jong, Y.

AU - Kirchhof, C. J. H. J.

AU - Kleijwegt, F. S.

AU - Klok, F. A.

AU - Kruip, M. J. H. A.

AU - Lenderink, T.

AU - Luermans, J. G.

AU - Meeder, J. G.

AU - Otten, A. M.

AU - Pisters, R.

AU - Pos, L.

AU - Prins, F. J.

AU - Römer, T. J.

AU - Smeets, F.

AU - Tahapary, G. J. M.

AU - Theunissen, L. J. H. J.

AU - Tieleman, R. G.

AU - Timmer, S. A. J.

AU - Tichelaar, V.

AU - Trines, S. A.

AU - van der Voort, P.

AU - Velthuis, S.

AU - de Vrey, E. A.

AU - Walhout, R. J.

AU - Hemels, M. E. W.

AU - Rutten, F. H.

AU - Geersing, G. J.

AU - Huisman, M. V.

PY - 2025/12/1

Y1 - 2025/12/1

N2 - 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.

AB - 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.

KW - Anticoagulants

KW - Atrial fibrillation

KW - Clinical decision rules

KW - Hemorrhage

KW - Validation study

UR - https://www.scopus.com/pages/publications/105022750420

U2 - 10.1016/j.thromres.2025.109533

DO - 10.1016/j.thromres.2025.109533

M3 - Article

C2 - 41240461

SN - 0049-3848

VL - 256

SP - 109533

JO - Thrombosis research

JF - Thrombosis research

M1 - 109533

ER -

Predicting clinically relevant bleeding in new-onset atrial fibrillation patients initiating oral anticoagulant therapy: External validation of the AF-BLEED score

Abstract

UN SDGs

Keywords

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