Association of Anticoagulant Therapy With Risk of Dementia Among Patients With Atrial Fibrillation

Daehoon Kim; Pil-Sung Yang; Eunsun Jang; Hee Tae Yu; Tae-Hoon Kim; Jae-Sun Uhm; Jong-Youn Kim; Jung-Hoon Sung; Hui-Nam Pak; Moon-Hyoung Lee; Gregory Y. H. Lip; Boyoung Joung


Europace. 2021;23(2):184-195. 

In This Article

Abstract and Introduction


Aims: To investigate the risk of dementia in atrial fibrillation (AF) patients treated with different oral anticoagulants (OACs).

Methods and results: This observational, population-based cohort study enrolled 53 236 dementia-free individuals with non-valvular AF who were aged ≥50 years and newly prescribed OACs from 1 January 2013 to 31 December 2016 from the Korean National Health Insurance Service database. Propensity score matching was used to compare the rates of dementia between users of non-vitamin K antagonist oral anticoagulant (NOAC) (dabigatran, rivaroxaban, and apixaban) and warfarin and to compare each individual NOAC with warfarin. Propensity score weighting analyses were also performed. In the study population (41.3% women; mean age: 70.7 years), 2194 had a diagnosis of incident dementia during a mean follow-up of 20.2 months. Relative to propensity-matched warfarin users, NOAC users tended to be at lower risk of dementia [hazard ratio (HR) 0.78, 95% confidence interval (CI) 0.69–0.90]. When comparing individual NOACs with warfarin, all the three NOACs were associated with lower dementia risk. In pairwise comparisons among NOACs, rivaroxaban was associated with decreased dementia risk, compared with dabigatran (HR 0.83, 95% CI 0.74–0.92). Supplemental propensity-weighted analyses showed consistent protective associations of NOACs with dementia relative to warfarin. The associations were consistent irrespectively of age, sex, stroke, and vascular disease and more prominent in standard dose users of NOAC.

Conclusion: In this propensity-matched and -weighted analysis using a real-world population-based cohort, use of NOACs was associated with lower dementia risk than use of warfarin among non-valvular AF patients initiating OAC treatment.


Approximately 40 million people worldwide have dementia.[1,2] Atrial fibrillation (AF), the most common sustained arrhythmia in elderly individuals, increases the risk of mortality and morbidity from stroke, heart failure, and comorbid chronic diseases.[3] Increasing evidence suggests that AF may also contribute to cognitive dysfunction and dementia, even without overt stroke.[4,5]

Recent observational studies have shown that oral anticoagulant (OAC) use may help to reduce the risk of dementia in patients with AF.[4,6–8] In AF patients receiving warfarin, a lower time-in-therapeutic range (TTR) has been associated with an increased risk of dementia.[8–10] Non-vitamin K antagonist oral anticoagulants (NOACs) may mitigate the difficulty of maintaining an appropriate TTR with a more predictable pharmacokinetic profile, and improved efficacy, safety, and convenience compared to warfarin.[11] However, randomised controlled trials of stroke prevention in AF patients using NOACs did not assess cognitive outcomes, and data investigating whether NOACs may reduce the risk of dementia compared with warfarin are scarce and inconclusive.[6,7,12–14]

We aimed to investigate the association of using NOACs (dabigatran, rivaroxaban, and apixaban) with risk of dementia, in comparison with warfarin, using a nationwide cohort of OAC-naïve patients with non-valvular AF and no prior neurological diagnoses.