CLINICAL INVESTIGATIONS Continued Use of Warfarin in Veterans with Atrial Fibrillation After Dementia Diagnosis Ariela R. Orkaby, MD,* † Al Ozonoff, PhD, ‡§ Joel I. Reisman, AB, ¶ Donald R. Miller, ScD, ¶ ** Shibei Zhao, MPH, ¶ and Adam J. Rose, MD, MSc ¶†† OBJECTIVES: To determine the effectiveness of warfarin in older adults with dementia. DESIGN: Retrospective cohort study. SETTING: Department of Veterans Affairs national healthcare system. PARTICIPANTS: Veterans aged 65 and older (73% aged ≥75, 99% male, 91% white) who had been receiving war- farin for nonvalvular atrial fibrillation for at least 6 months, were newly diagnosed with dementia in fiscal year 2007 or 2008, and were not enrolled in Medicare Advantage (n = 2,572). MEASUREMENTS: The onset of dementia was defined according to International Classification of Diseases, Ninth Revision, code. Participants were followed for up to 4 years for persistence of warfarin therapy, anticoagula- tion control, major hemorrhage, ischemic stroke, and all- cause mortality. RESULTS: The average CHADS2 score was 3.3 Æ 1.3. After a diagnosis of dementia, 405 individuals (16%) per- sisted on warfarin therapy. Unadjusted Cox proportional hazards analysis demonstrated a protective effect of war- farin in prevention of ischemic stroke (hazard ratio (HR) = 0.64, 95% confidence interval (CI) = 0.46–0.89, P = .008), major bleeding (HR = 0.72, 95% CI = 0.55– 0.94, P = .02), and all-cause mortality (HR = 0.66, 95% CI = 0.55–0.79, P < .001). Using propensity score match- ing, the protective effect of continuing warfarin persisted in prevention of stroke (HR = 0.74, 95% CI = 0.54– 0.996, P = .047) and mortality (HR = 0.72, 95% CI = 0.60–0.87, P < .001), with no statistically significant decrease in risk of major bleeding (HR = 0.78, 95% CI = 0.61–1.01, P = .06). CONCLUSION: Discontinuing warfarin after a diagnosis of dementia is associated with a significant increase in stroke and mortality. J Am Geriatr Soc 2016. Key words: atrial fibrillation; dementia; warfarin A trial fibrillation (AF) is a common disease in older adults, affecting one in 25 adults aged 60 and older and up to one in 10 adults 80 years and older. 1 Anticoag- ulation is the mainstay of therapy to prevent stroke, the most-feared outcome associated with AF. Millions of peo- ple around the world take the oral vitamin K antagonist warfarin to prevent and treat thromboembolic events. 2 Despite the approval of novel anticoagulants, millions of individuals will continue to take warfarin for the foresee- able future. The majority of individuals who take warfarin are aged 65 and older. 3 Another condition that commonly affects older adults is dementia. It is estimated that 24.3 million people have dementia worldwide, 4 a number that will also grow as the population ages. Predictably, many older adults have dementia and AF, but little is known about how best to manage these individuals. The natural history of individu- als with AF taking warfarin who then develop dementia is not well understood, which may contribute to the under- use of anticoagulants in older adults with AF. 5,6 This study used a large, detailed database of individu- als receiving oral anticoagulation from the Department of Veterans Affairs (VA) to explore these questions. Individu- als who had previously been receiving warfarin for AF and then received a new diagnosis of dementia were identified and tracked for up to 4 years. The outcomes of persistence of warfarin therapy, anticoagulation control, major hemor- rhage, stroke, and all-cause mortality were examined. From the *Geriatric Research, Education, and Clinical Center (GRECC), Veterans Affairs Boston Healthcare System; † Division of Aging, Brigham and Women’s Hospital, Harvard Medical School; ‡ Center for Patient Safety and Quality Research, Boston Children’s Hospital; § Department of Pediatrics, Harvard Medical School; ¶ Center for Healthcare Organization and Implementation Research, Bedford Veterans Affairs Medical Center; **School of Public Health, Boston University; and †† Department of Medicine, Section of Internal Medicine, Boston University Medical Center, Boston, Massachusetts. An earlier version of this work was presented as a poster at the American Geriatric Society meeting, May 2014, in Orlando, Florida. Address correspondence to Dr. Ariela R. Orkaby, Division of Aging, Brigham and Women’s Hospital, 1620 Tremont Street, Boston, MA 02120. E-mail: aorkaby@partners.org DOI: 10.1111/jgs.14573 JAGS 2016 © 2016, Copyright the Authors Journal compilation © 2016, The American Geriatrics Society 0002-8614/16/$15.00