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Biomarker-Based ABC-AF Risk Scores for Personalized Treatment to Reduce Stroke or Death in Atrial Fibrillation : A Registry-Based, Multicenter, Randomized, Controlled Study

Oldgren, Jonas ; Hijazi, Ziad ; Arheden, Håkan LU ; Björkenheim, Anna ; Frykman, Viveka ; Janzon, Magnus ; Ravn-Fischer, Annica ; Renlund, Henrik ; Själander, Anders and Åkerfeldt, Torbjörn , et al. (2025) In Circulation 152(21). p.1457-1469
Abstract

BACKGROUND: – The clinical use of risk scores to guide treatment decisions and improve clinical outcomes has rarely been prospectively evaluated. This study aimed to evaluate whether a biomarker-based ABC-AF risk score–guided multidimensional treatment strategy improves long-term outcomes in patients with AF. METHODS: – The multicenter, registry-based, randomized, controlled, open-label study enrolled adults with AF. In the ABC-AF strategy arm, the investigator was informed of each individual’s ABC-AF score risks for stroke and bleeding, which were used as decision support to tailor treatment recommendations, including preference for type of direct oral anticoagulant treatment. In the standard of care arm, patient management was at the... (More)

BACKGROUND: – The clinical use of risk scores to guide treatment decisions and improve clinical outcomes has rarely been prospectively evaluated. This study aimed to evaluate whether a biomarker-based ABC-AF risk score–guided multidimensional treatment strategy improves long-term outcomes in patients with AF. METHODS: – The multicenter, registry-based, randomized, controlled, open-label study enrolled adults with AF. In the ABC-AF strategy arm, the investigator was informed of each individual’s ABC-AF score risks for stroke and bleeding, which were used as decision support to tailor treatment recommendations, including preference for type of direct oral anticoagulant treatment. In the standard of care arm, patient management was at the discretion of the investigator. Primary outcome was a composite of stroke or death. Secondary outcomes included stroke, death, major bleeding events, and their composite outcome. RESULTS: – The intention-to-treat population comprised 3933 patients with a median age of 73.7 years; 33.6% were women, 51.3% had paroxysmal AF, 11.2% had a previous stroke or transient ischemic attack, and 85.7% had oral anticoagulant treatment. After randomization, 97.8% in the ABC-AF strategy arm and 92.6% in the standard of care arm received OACs (P<0.0001). Enrollment was prematurely terminated owing to safety concerns with a trend toward higher mortality in patients with CHA2DS2-VASc scores of ≥3, and the study was therefore underpowered for its primary objective. Over a median follow-up of 2.6 years, 175 primary events (3.18/100 patient-years [100PY]) occurred in the ABC-AF strategy and 148 (2.67/100PY) in the standard of care arm (hazard ratio [HR], 1.19 [95% CI, 0.96–1.48]; P=0.12). Major bleeding events were 152 (2.82/100PY) versus 141 (2.61/100PY; HR, 1.08 [95% CI, 0.86–1.36]; P=0.50), stroke 48 (0.87/100PY) versus 41 (0.74/100PY; HR, 1.18 [95% CI, 0.78–1.79]; P=0.44), death 136 (2.44/100PY) versus 113 (2.02/100PY; HR, 1.21 [95% CI, 0.94–1.55]; P=0.13), and rates of composite stroke, death, or major bleeding 277 (5.21/100PY) versus 244 (4.55/100PY; HR, 1.14 [95% CI, 0.96–1.36]; P=0.13). Primary outcome results were similar across ABC-AF score subgroups (interaction P=0.98). CONCLUSIONS: – The individually tailored multidimensional treatment strategy, based on ABC-AF risk scores, did not improve clinical outcomes compared with usual guideline-based care in patients with AF. The results emphasize the need for prospective testing of the use of risk stratification and precision medicine tools in different clinical settings before implementation in routine care. REGISTRATION: – URL: https://www.clinicaltrials.gov; Unique identifier: NCT03753490.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
atrial fibrillation, biomarkers, intracranial hemorrhages, risk factors, stroke
in
Circulation
volume
152
issue
21
pages
13 pages
publisher
Lippincott Williams & Wilkins
external identifiers
  • scopus:105027397591
  • pmid:40884774
ISSN
0009-7322
DOI
10.1161/CIRCULATIONAHA.125.076725
language
English
LU publication?
yes
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Publisher Copyright: © 2025
id
edab97cf-b47e-4333-9235-30828a3ce054
date added to LUP
2026-02-16 14:16:30
date last changed
2026-02-17 03:00:07
@article{edab97cf-b47e-4333-9235-30828a3ce054,
  abstract     = {{<p>BACKGROUND: – The clinical use of risk scores to guide treatment decisions and improve clinical outcomes has rarely been prospectively evaluated. This study aimed to evaluate whether a biomarker-based ABC-AF risk score–guided multidimensional treatment strategy improves long-term outcomes in patients with AF. METHODS: – The multicenter, registry-based, randomized, controlled, open-label study enrolled adults with AF. In the ABC-AF strategy arm, the investigator was informed of each individual’s ABC-AF score risks for stroke and bleeding, which were used as decision support to tailor treatment recommendations, including preference for type of direct oral anticoagulant treatment. In the standard of care arm, patient management was at the discretion of the investigator. Primary outcome was a composite of stroke or death. Secondary outcomes included stroke, death, major bleeding events, and their composite outcome. RESULTS: – The intention-to-treat population comprised 3933 patients with a median age of 73.7 years; 33.6% were women, 51.3% had paroxysmal AF, 11.2% had a previous stroke or transient ischemic attack, and 85.7% had oral anticoagulant treatment. After randomization, 97.8% in the ABC-AF strategy arm and 92.6% in the standard of care arm received OACs (P&lt;0.0001). Enrollment was prematurely terminated owing to safety concerns with a trend toward higher mortality in patients with CHA<sub>2</sub>DS<sub>2</sub>-VASc scores of ≥3, and the study was therefore underpowered for its primary objective. Over a median follow-up of 2.6 years, 175 primary events (3.18/100 patient-years [100PY]) occurred in the ABC-AF strategy and 148 (2.67/100PY) in the standard of care arm (hazard ratio [HR], 1.19 [95% CI, 0.96–1.48]; P=0.12). Major bleeding events were 152 (2.82/100PY) versus 141 (2.61/100PY; HR, 1.08 [95% CI, 0.86–1.36]; P=0.50), stroke 48 (0.87/100PY) versus 41 (0.74/100PY; HR, 1.18 [95% CI, 0.78–1.79]; P=0.44), death 136 (2.44/100PY) versus 113 (2.02/100PY; HR, 1.21 [95% CI, 0.94–1.55]; P=0.13), and rates of composite stroke, death, or major bleeding 277 (5.21/100PY) versus 244 (4.55/100PY; HR, 1.14 [95% CI, 0.96–1.36]; P=0.13). Primary outcome results were similar across ABC-AF score subgroups (interaction P=0.98). CONCLUSIONS: – The individually tailored multidimensional treatment strategy, based on ABC-AF risk scores, did not improve clinical outcomes compared with usual guideline-based care in patients with AF. The results emphasize the need for prospective testing of the use of risk stratification and precision medicine tools in different clinical settings before implementation in routine care. REGISTRATION: – URL: https://www.clinicaltrials.gov; Unique identifier: NCT03753490.</p>}},
  author       = {{Oldgren, Jonas and Hijazi, Ziad and Arheden, Håkan and Björkenheim, Anna and Frykman, Viveka and Janzon, Magnus and Ravn-Fischer, Annica and Renlund, Henrik and Själander, Anders and Åkerfeldt, Torbjörn and Wallentin, Lars}},
  issn         = {{0009-7322}},
  keywords     = {{atrial fibrillation; biomarkers; intracranial hemorrhages; risk factors; stroke}},
  language     = {{eng}},
  month        = {{11}},
  number       = {{21}},
  pages        = {{1457--1469}},
  publisher    = {{Lippincott Williams & Wilkins}},
  series       = {{Circulation}},
  title        = {{Biomarker-Based ABC-AF Risk Scores for Personalized Treatment to Reduce Stroke or Death in Atrial Fibrillation : A Registry-Based, Multicenter, Randomized, Controlled Study}},
  url          = {{http://dx.doi.org/10.1161/CIRCULATIONAHA.125.076725}},
  doi          = {{10.1161/CIRCULATIONAHA.125.076725}},
  volume       = {{152}},
  year         = {{2025}},
}