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Efficacy of Warfarin Anticoagulation and Incident Dementia in a Community-Based Cohort of Atrial Fibrillation

Published:January 09, 2018DOI:



      To study the association between time in therapeutic range (TTR) during warfarin therapy and risk of dementia in a population-based cohort of incident atrial fibrillation (AF).

      Patients and Methods

      We conducted an observational population-based study of 2800 nondemented patients with incident AF from January 1, 2000, through December 31, 2010. The association of incident dementia with warfarin therapy and TTR was examined using Cox proportional hazards regression models.


      Mean patient age was 71.2 years; 53% were men (n=1495), and warfarin was prescribed to 50.5% (n=1414) within 90 days of AF diagnosis. Incident dementia diagnosis occurred in 357 patients (12.8%) over a mean ± SD follow-up of 5.0±3.7 years. After adjusting for confounders, warfarin therapy was associated with a reduced incidence of dementia (hazard ratio [HR], 0.80; 95% CI, 0.64-0.99). However, only those in the 2 highest quartiles of TTR were associated with lower risk of dementia. A 10% increase in TTR with a 10% reduction in time spent in the subtherapeutic (HR, 0.71; 95% CI, 0.64-0.79) and supratherapeutic (HR, 0.67; 95% CI, 0.57-0.79) ranges were associated with decreased risk of dementia.


      In the community, warfarin therapy for AF is associated with a 20% reduction in risk of dementia. Increasing TTR on warfarin is associated with reduced risk of dementia. The risk of dementia was reduced with a reduction in time spent in subtherapeutic and supratherapeutic international normalized ratio range. Effective anticoagulation may prevent cognitive impairment in patients with AF.

      Abbreviations and Acronyms:

      AF (atrial fibrillation), CHA2DS2-VASc (congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, stroke/transient ischemic attack, vascular disease, age 65 to 74 years, sex category), HR (hazard ratio), ICD-9 (International Classification of Diseases, Ninth Revision), INR (international normalized ratio), MRI (magnetic resonance imaging), TIA (transient ischemic attack), TTR (time in therapeutic range)
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      Linked Article

      • Efficacy of Warfarin Anticoagulation and Incident Dementia: Does Cognitive Impairment Reduce Efficacy?
        Mayo Clinic ProceedingsVol. 93Issue 11
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          The data in the article by Madhavan et al1 published in the February 2018 issue of Mayo Clinic Proceedings point toward reverse causality relative to that inferred by the authors, that is, that the development of dementia causes patients to fail to maintain a therapeutic range of anticoagulation. First, the time in therapeutic range (TTR) for patients developing dementia when measured more than 1 year before the diagnosis of dementia was comparable to that for patients who did not develop dementia.
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