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Outcomes in a Warfarin-Treated Population With Atrial Fibrillation
Open accessAbstract
IMPORTANCE: Vitamin K antagonist (eg, warfarin) use is nowadays challenged by the non-vitamin K antagonist oral anticoagulants (NOACs) for stroke prevention in atrial fibrillation (AF). NOAC studies were based on comparisons with warfarin arms with times in therapeutic range (TTRs) of 55.2% to 64.9%, making the results less credible in health care systems with higher TTRs. OBJECTIVES: To evaluate the efficacy and safety of well-managed warfarin therapy in patients with nonvalvular AF, the risk of complications, especially intracranial bleeding, in patients with concomitant use of aspirin, and the impact of international normalized ratio (INR) control. DESIGN, SETTING, AND PARTICIPANTS: A retrospective, multicenter cohort study based on Swedish registries, especially AuriculA, a quality register for AF and oral anticoagulation, was conducted. The register contains nationwide data, including that from specialized anticoagulation clinics and primary health care centers. A total of 40 449 patients starting warfarin therapy owing to nonvalvular AF during the study period were monitored until treatment cessation, death, or the end of the study. The study was conducted from January 1, 2006, to December 31, 2011, and data were analyzed between February 1 and November 15, 2015. Associating complications with risk factors and individual INR control, we evaluated the efficacy and safety of warfarin treatment in patients with concomitant aspirin therapy and those with no additional antiplatelet medications. EXPOSURES: Use of warfarin with and without concomitant therapy with aspirin. MAIN OUTCOMES AND MEASURES: Annual incidence of complications in association with individual TTR (iTTR), INR variability, and aspirin use and identification of factors indicating the probability of intracranial bleeding. RESULTS: Of the 40 449 patients included in the study, 16 201 (40.0%) were women; mean (SD) age of the cohort was 72.5 (10.1) years, and the mean CHA2DS2-VASc (cardiac failure or dysfunction, hypertension, age ≥75 years [doubled], diabetes mellitus, stroke [doubled]-vascular disease, age 65-74 years, and sex category [female]) score was 3.3 at baseline. The annual incidence, reported as percentage (95% CI) of all-cause mortality was 2.19% (2.07-2.31) and, for intracranial bleeding, 0.44% (0.39-0.49). Patients receiving concomitant aspirin had annual rates of any major bleeding of 3.07% (2.70-3.44) and thromboembolism of 4.90% (4.43-5.37), and those with renal failure were at higher risk of intracranial bleeding (hazard ratio, 2.25; 95% CI, 1.32-3.82). Annual rates of any major bleeding and any thromboembolism in iTTR less than 70% were 3.81% (3.51-4.11) and 4.41% (4.09-4.73), respectively, and, in high INR variability, were 3.04% (2.85-3.24) and 3.48% (3.27-3.69), respectively. For patients with iTTR 70% or greater, the level of INR variability did not alter event rates. CONCLUSIONS AND RELEVANCE: Well-managed warfarin therapy is associated with a low risk of complications and is still a valid alternative for prophylaxis of AF-associated stroke. Therapy should be closely monitored for patients with renal failure, concomitant aspirin use, and poor INR control.
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“TTR on VKA therapy is an important predictor of major haemorrhage.432,441,494”
From 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS (2016) · cites this paper as [494]
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Rivaroxaban versus warfarin in nonvalvular atrial fibrillation
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Apixaban versus warfarin in patients with atrial fibrillation
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2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS
Kirchhof, P. F., Benussi, S., Kotecha, D., Ahlsson, A., Atar, D., Casadei, B., Castellà, M., Diener, H., Heidbüchel, H., Hendriks, J., et al. (2016) · EP Europace · doi:10.1093/europace/euw295 · Cited by 6,438
Self-citation2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS
Kirchhof, P., Benussi, S., Kotecha, D., Ahlsson, A., Atar, D., Casadei, B., Castella, M., Diener, H.-C., Heidbuchel, H., Hendriks, J., et al. (2016) · European Heart Journal · doi:10.1093/eurheartj/ehw210 · Cited by 6,418
Self-citation2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS
Kirchhof, P., Benussi, S., Kotecha, D., Ahlsson, A., Atar, D., Casadei, B., Castella, M., Diener, H.-C., Heidbuchel, H., Hendriks, J., et al. (2016) · European Journal of Cardio-Thoracic Surgery · doi:10.1093/ejcts/ezw313 · Cited by 1,403
Self-citationAntithrombotic Therapy for Atrial Fibrillation
Lip, G. Y. H., Banerjee, A., Boriani, G., Chiang, C. E., Fargo, R. A., Freedman, B., Lane, D. A., Ruff, C. T., Turakhia, M. P., Werring, D. J., et al. (2018) · CHEST Journal · doi:10.1016/j.chest.2018.07.040 · Cited by 963
Self-citationStroke prevention in atrial fibrillation
Freedman, B., Potpara, T., & Lip, G. Y. H. (2016) · The Lancet · doi:10.1016/s0140-6736(16)31257-0 · Cited by 484
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Metadata
- Authors
- Björck, F., Renlund, H., Lip, G. Y. H., Wester, P., Svensson, P. J., & Själander, A.
- Affiliations
- Umeå University (SE)
- Uppsala University (SE)
- University of Birmingham (GB)
- Danderyds sjukhus (SE)
- Lund University (SE)
- Corresponding author
- Björck, Fredrik
- Venue
- JAMA Cardiology
- Publisher
- American Medical Association (AMA)
- Published
- 2016-05-01
- Volume
- 1
- Issue
- 2
- Pages
- 172
- ISSN
- 2380-6583 (ISSN-L)
- OpenAlex
- W2338123562
- Cited by
- 153
- References
- 40
- Citations by year
- 2026: 8 · 2025: 7 · 2024: 12 · 2023: 7 · 2022: 11 · 2021: 14 · 2020: 15 · 2019: 21 · 2018: 23 · 2017: 22 · 2016: 13
- FWCI
- 21.72
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- JAMA Cardiology (publishedVersion)
- PubMed (publishedVersion)
- VBN Forskningsportal (Aalborg Universitet) (submittedVersion, other-oa)
- 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 › Clinical Neurology › Acute Ischemic Stroke Management
- Keywords
- warfarin, atrial fibrillation, non-valvular atrial fibrillation, time in therapeutic range, INR variability, aspirin, intracranial hemorrhage, stroke prevention, oral anticoagulation, antiplatelet therapy, bleeding risk, CHA2DS2-VASc score, direct oral anticoagulants, treatment outcomes, auricle
- MeSH terms
- Aged, Aged, 80 and over, Anticoagulants, Aspirin, Atrial Fibrillation, Female, Hemorrhage, Humans, Male, Middle Aged, Platelet Aggregation Inhibitors, Retrospective Studies, Risk Factors, Sweden, Thromboembolism, Warfarin, Treatment Outcome, International Normalized Ratio, Stroke
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