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Residual Stroke Risk Among Patients With Atrial Fibrillation Prescribed Oral Anticoagulants : A Patient-Level Meta-Analysis From COMBINE AF

Johnson, Linda S. LU ; Benz, Alexander P. ; Shoamanesh, Ashkan ; Eikelboom, John W. ; Ezekowitz, Michael ; Giugliano, Robert P. ; Wallentin, Lars ; Ruff, Christian T. ; Lopes, Renato D. and Jolly, Sanjit , et al. (2024) In Journal of the American Heart Association 13(17).
Abstract

BACKGROUND: Despite oral anticoagulation, patients with atrial fibrillation (AF) remain at risk of ischemic stroke and systemic embolism (SE) events. For patients whose residual risk is sufficiently high, additional therapies might be useful to mitigate stroke risk. METHODS AND RESULTS: Individual patient data from 5 landmark trials testing oral anticoagulation in AF were pooled in A Collaboration Between Multiple Institutions to Better Investigate Non-Vitamin K Antagonist Oral Anticoagulant Use in AF (COMBINE AF). We calculated the rate of ischemic stroke/SE among oral anticoagulation–treated patients with a CHA2 DS2 VASc score≥2, across strata of CHA2 DS2-VASc score, stroke history, and AF... (More)

BACKGROUND: Despite oral anticoagulation, patients with atrial fibrillation (AF) remain at risk of ischemic stroke and systemic embolism (SE) events. For patients whose residual risk is sufficiently high, additional therapies might be useful to mitigate stroke risk. METHODS AND RESULTS: Individual patient data from 5 landmark trials testing oral anticoagulation in AF were pooled in A Collaboration Between Multiple Institutions to Better Investigate Non-Vitamin K Antagonist Oral Anticoagulant Use in AF (COMBINE AF). We calculated the rate of ischemic stroke/SE among oral anticoagulation–treated patients with a CHA2 DS2 VASc score≥2, across strata of CHA2 DS2-VASc score, stroke history, and AF type, as either paroxysmal or nonparoxysmal. We included 71 794 patients with AF (median age 72 years, interquartile range, 13 years, 61.3% male) randomized to a direct oral anticoagulant or vitamin K antagonist, and followed for a mean of 2.1 (±0.8) years. The median CHA2 DS2-VASc score was 4 (interquartile range, 3–5), 18.8% had a prior stroke, and 76.4% had nonparoxysmal AF. The overall rate of stroke/SE was 1.33%/y (95% CI, 1.27–1.39); 1.38%/y (95% CI, 1.31–1.45) for nonparoxysmal AF, and 1.15%/y (95% CI, 1.05–1.27) for paroxysmal AF. The rate of ischemic stroke/SE increased by a rate ratio of 1.36 (95% CI, 1.32–1.41) per 1-point increase in CHA2 DS2-VASc, reaching 1.67%/y (95% CI, 1.59–1.75) ≥4 CHA2 DS2-VASc points. Patients with both nonparoxysmal AF and CHA2 DS2-VASc ≥4 had a stroke/SE rate of 1.75%/y (95% CI, 1.66–1.85). In patients with a prior stroke, the risk was 2.51%/y (95% CI, 2.33–2.71). CONCLUSIONS: AF type, CHA2 DS2-VASc score, and stroke history can identify patients with AF, who despite oral anticoagulation have a residual stroke/SE risk of 1.5% to 2.5% per year. Evaluation of additional stroke/SE prevention strategies in high-risk patients is warranted.

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publishing date
type
Contribution to journal
publication status
published
subject
keywords
anticoagulation, atrial fibrillation, stroke
in
Journal of the American Heart Association
volume
13
issue
17
article number
e034758
publisher
Wiley-Blackwell
external identifiers
  • pmid:39190578
  • scopus:85203203392
ISSN
2047-9980
DOI
10.1161/JAHA.123.034758
language
English
LU publication?
yes
id
71e17b2b-6e9a-4fed-8b42-d24254588765
date added to LUP
2024-11-22 12:04:44
date last changed
2025-07-05 20:36:11
@article{71e17b2b-6e9a-4fed-8b42-d24254588765,
  abstract     = {{<p>BACKGROUND: Despite oral anticoagulation, patients with atrial fibrillation (AF) remain at risk of ischemic stroke and systemic embolism (SE) events. For patients whose residual risk is sufficiently high, additional therapies might be useful to mitigate stroke risk. METHODS AND RESULTS: Individual patient data from 5 landmark trials testing oral anticoagulation in AF were pooled in A Collaboration Between Multiple Institutions to Better Investigate Non-Vitamin K Antagonist Oral Anticoagulant Use in AF (COMBINE AF). We calculated the rate of ischemic stroke/SE among oral anticoagulation–treated patients with a CHA<sub>2</sub> DS<sub>2</sub> VASc score≥2, across strata of CHA<sub>2</sub> DS<sub>2</sub>-VASc score, stroke history, and AF type, as either paroxysmal or nonparoxysmal. We included 71 794 patients with AF (median age 72 years, interquartile range, 13 years, 61.3% male) randomized to a direct oral anticoagulant or vitamin K antagonist, and followed for a mean of 2.1 (±0.8) years. The median CHA<sub>2</sub> DS<sub>2</sub>-VASc score was 4 (interquartile range, 3–5), 18.8% had a prior stroke, and 76.4% had nonparoxysmal AF. The overall rate of stroke/SE was 1.33%/y (95% CI, 1.27–1.39); 1.38%/y (95% CI, 1.31–1.45) for nonparoxysmal AF, and 1.15%/y (95% CI, 1.05–1.27) for paroxysmal AF. The rate of ischemic stroke/SE increased by a rate ratio of 1.36 (95% CI, 1.32–1.41) per 1-point increase in CHA<sub>2</sub> DS<sub>2</sub>-VASc, reaching 1.67%/y (95% CI, 1.59–1.75) ≥4 CHA<sub>2</sub> DS<sub>2</sub>-VASc points. Patients with both nonparoxysmal AF and CHA<sub>2</sub> DS<sub>2</sub>-VASc ≥4 had a stroke/SE rate of 1.75%/y (95% CI, 1.66–1.85). In patients with a prior stroke, the risk was 2.51%/y (95% CI, 2.33–2.71). CONCLUSIONS: AF type, CHA<sub>2</sub> DS<sub>2</sub>-VASc score, and stroke history can identify patients with AF, who despite oral anticoagulation have a residual stroke/SE risk of 1.5% to 2.5% per year. Evaluation of additional stroke/SE prevention strategies in high-risk patients is warranted.</p>}},
  author       = {{Johnson, Linda S. and Benz, Alexander P. and Shoamanesh, Ashkan and Eikelboom, John W. and Ezekowitz, Michael and Giugliano, Robert P. and Wallentin, Lars and Ruff, Christian T. and Lopes, Renato D. and Jolly, Sanjit and Whitlock, Richard and Granger, Christopher B. and Connolly, Stuart and Healey, Jeffrey S.}},
  issn         = {{2047-9980}},
  keywords     = {{anticoagulation; atrial fibrillation; stroke}},
  language     = {{eng}},
  number       = {{17}},
  publisher    = {{Wiley-Blackwell}},
  series       = {{Journal of the American Heart Association}},
  title        = {{Residual Stroke Risk Among Patients With Atrial Fibrillation Prescribed Oral Anticoagulants : A Patient-Level Meta-Analysis From COMBINE AF}},
  url          = {{http://dx.doi.org/10.1161/JAHA.123.034758}},
  doi          = {{10.1161/JAHA.123.034758}},
  volume       = {{13}},
  year         = {{2024}},
}