Risks of thromboembolism and bleeding with thromboprophylaxis in patients with atrial fibrillation: A net clinical benefit analysis using a ‘real world’ nationwide cohort study
Abstract
It was the aim of this study to determine the efficacy and safety of vitamin K antagonists (VKAs) and acetylsalicylic acid (ASA) in patients with non-valvular atrial fibrillation (AF), with separate analyses according to predicted thromboembolic and bleeding risk. By individual level-linkage of nationwide registries, we identified all patients discharged with non-valvular AF in Denmark (n=132,372). For every patient, the risk of stroke and bleeding was calculated by CHADS₂, CHA₂DS₂-VASc, and HAS-BLED. During follow-up, treatment with VKA and ASA was determined time-dependently. VKA consistently lowered the risk of thromboembolism compared to ASA and no treatment; the combination of VKA+ASA did not yield any additional benefit. In patients at high thromboembolic risk, hazard ratios (95% confidence interval) for thromboembolism were: 1.81 (1.73-1.90), 1.14 (1.06-1.23), and 1.86 (1.78-1.95) for ASA, VKA+ASA, and no treatment, respectively, compared to VKA. The risk of bleeding was increased with VKA, ASA, and VKA+ASA compared to no treatment, the hazard ratios were: 1.0 (VKA; reference), 0.93 (ASA; 0.89-0.97), 1.64 (VKA+ASA; 1.55-1.74), and 0.84 (no treatment; 0.81-0.88), respectively. There was a neutral or positive net clinical benefit (ischaemic stroke vs. intracranial haemorrhage) with VKA alone in patients with a CHADS₂ score of ≥ 0, and CHA₂DS₂-VASc score of ≥ 1. This large cohort study confirms the efficacy of VKA and no effect of ASA treatment on the risk of stroke/thromboembolism. Also, the risk of bleeding was increased with both VKA and ASA treatment, but the net clinical benefit was clearly positive, in favour of VKA in patients with increased risk of stroke/thromboembolism.
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The evidence supporting antiplatelet monotherapy for stroke prevention in AF is very limited.
“The evidence supporting antiplatelet monotherapy for stroke prevention in AF is very limited.38,[428][429][430]”
From 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS (2016) · cites this paper as [429]
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- Authors
- Lip, G., Lindhardsen, J., Lane, D., Ahlehoff, O., Hansen, M., Raunsø, J., Tolstrup, J., Hansen, P., Gislason, G., Torp-Pedersen, C., & Olesen, J.
- Affiliations
- Birmingham City Hospital (GB)
- Gentofte Hospital (DK)
- Danish National Institute of Public Health (DK)
- ORCID
- Venue
- Thrombosis and Haemostasis
- Publisher
- Georg Thieme Verlag KG
- Published
- 2011
- Volume
- 106
- Issue
- 10
- Pages
- 739-749
- ISSN
- 0340-6245 (ISSN-L)
- 2567-689X
- OpenAlex
- W2143255011
- Cited by
- 428
- References
- 37
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 5 · 2023: 10 · 2022: 7 · 2021: 12 · 2020: 18 · 2019: 19 · 2018: 31 · 2017: 30 · 2016: 43 · 2015: 56 · 2014: 43 · 2013: 70 · 2012: 62
- FWCI
- 41.77
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Thrombosis and Haemostasis (publishedVersion)
- PubMed (publishedVersion)
- University of Southern Denmark Research Portal (University of Southern Denmark) (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
- University of Birmingham Research Portal (University of Birmingham) (submittedVersion)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Atrial Fibrillation Management and Outcomes
- Health Sciences › Medicine › Internal Medicine › Venous Thromboembolism Diagnosis and Management
- Health Sciences › Medicine › Epidemiology › Acute Ischemic Stroke Management
- Keywords
- atrial fibrillation, thromboprophylaxis, vitamin K antagonists, aspirin, bleeding risk, thromboembolism, stroke prevention, net clinical benefit, CHADS2 score, CHA2DS2-VASc score, HAS-BLED score, intracranial hemorrhage, combination anticoagulant therapy
- MeSH terms
- Aged, Aged, 80 and over, Aspirin, Atrial Fibrillation, Denmark, Drug Evaluation, Female, Fibrinolytic Agents, Follow-Up Studies, Hemorrhage, Humans, Male, Middle Aged, Registries, Thromboembolism, Vitamin K, Cohort Studies, Risk Assessment
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