64Risk of dementia in patients treated with non-vitamin k antagonist oral anticoagulant or warfarin for nonvalvular atrial fibrillation

Abstract Background Evidence is accumulating that use of oral anticoagulants (OACs) decreases the risk of dementia in patients with atrial fibrillation (AF), but it is unclear if there is a difference between non-vitamin K antagonist oral anticoagulants (NOACs) and warfarin in protecting against dementia. Purpose To compare the risk of dementia between patients taking either NOAC or warfarin using a nationwide cohort data covering the entire Korean population. Methods Using the Korean national health insurance service database, 68,984 new OAC users with non-valvular AF aged ≥50 years and no prior diagnosis of dementia were identified during the period of 2013–2016 (39,687 NOAC users and 29,297 warfarin users). Starting from OAC initiation, participants were followed up until the date of dementia, death, or December 31, 2016. We compared the rates of dementia in 1:1 propensity score-matched cohorts of NOAC (n=18,925) and warfarin users (n=18,925). Results During the 52,259 person-years of follow-up, there were 2,750 dementia events. Use of NOAC was associated with significant lower risk of dementia [hazard ratio (HR) 0.75, 95% confidence interval (CI) 0.69–0.81], compared with warfarin. The risk reduction was prominent for vascular dementia (HR 0.60, 95% CI 0.52–0.71), whereas there was no significant difference in the risk of Alzheimer dementia (HR 0.92, 95% CI 0.83–1.02). Restricting the analyses to patients with no stroke diagnosis prior to OAC initiation (primary prevention) showed no significant difference between NOAC and warfarin in any types of dementia, but in the subgroup with prior stroke (secondary prevention), NOAC significantly reduced the risk of overall (HR 0.70, 95% CI 0.63–0.78) and vascular dementia (HR 0.59, 95% CI 0.49–0.69). Subgroup analysis according to stroke Hx Patient N Overall dementia Alzheimer dementia Vascular dementia HR (95% CI) P for interaction HR (95% CI) P for interaction HR (95% CI) P for interaction Total 37,850 0.75 (0.69–0.81) 0.92 (0.83–1.02) 0.60 (0.52–0.71) Without prior stroke 24,773 0.90 (0.78–1.05) 0.948 0.98 (0.83–1.15) 0.235 0.85 (0.56–1.28) 0.863 With prior stroke 13,077 0.70 (0.63–0.78) 0.90 (0.79–1.03) 0.59 (0.49–0.69) CI, confidence interval; HR, hazard ratio. KM curves of dementia incidence Conclusion In this propensity-weighted nationwide cohort of non-valvular AF patients, NOAC was associated with reduced risk of dementia, compared with warfarin. This association was the most pronounced for vascular dementia in patients with prior stroke. Acknowledgement/Funding The Korean Ministry of Education, Science and Technology (NRF-2017R1A2B3003303) and the Korean Ministry of Health & Welfare (HI16C0058, HI15C1200)