Abstract
Objective
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.
Results
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.
Conclusion
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)To read this article in full you will need to make a payment
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Article Info
Publication History
Published online: January 09, 2018
Footnotes
For editorial comment, see page 127
Grant Support: This study was made possible by the Rochester Epidemiology Project (grant number R01-AG034676; Principal Investigators: Walter A. Rocca, MD, MPH and Jennifer L. St Sauver, PhD). This work was supported by grant 11SDG7260039 from the American Heart Association and by grant R01 AG034676 from the National Institute on Aging awarded to Dr Alanna M Chamberlain . The funding sources played no role in the design, conduct, or reporting of this study.
Potential Competing Interests: The authors report no competing interests.
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- Efficacy of Warfarin Anticoagulation and Incident Dementia: Does Cognitive Impairment Reduce Efficacy?Mayo Clinic ProceedingsVol. 93Issue 11
- PreviewThe 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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