Nonvitamin K Antagonist Oral Anticoagulants Versus Warfarin in Atrial Fibrillation Patients and Risk of Dementia: A Nationwide Propensity‐Weighted Cohort Study

Abstract

Background It is unclear whether nonvitamin K antagonist oral anticoagulants ( NOAC s) can mitigate dementia development in atrial fibrillation. We compared dementia development among users of NOACs or warfarin in patients with atrial fibrillation with no prior neurological diagnoses. Methods and Results We conducted a Danish nationwide cohort study including 33 617 new oral anticoagulant users with nonvalvular atrial fibrillation, of which 11 052 were aged 60 to 69 years, 13 237 were aged 70 to 79 years, and 9238 were aged 80 years and older. To exclude prevalent non ‐oral anticoagulants– associated dementia, we considered the at‐risk population of patients alive and free of dementia at 180 days following inclusion. We compared rates of new‐onset dementia by age and treatment regimen using inverse probability of treatment weighting to account for confounding. Approximately 60% of patients were NOAC users and 40% were warfarin users. Mean follow‐up was 3.4 years. Dementia occurred in 41 patients aged 60 to 69 years, 276 patients aged 70 to 79 years, and 441 patients aged 80 years and older. Relative to warfarin users, dementia rates were nonsignificantly lower among NOAC users aged 60 to 69 years (0.11 events/100 person‐years versus 0.12 events/100 person‐years; weighted hazard ratio, 0.92 [95% CI, 0.48–1.72]) and NOAC users aged 70 to 79 years (0.64 events/100 person‐years versus 0.78 events/100 person‐years; weighted hazard ratio , 0.86 [95% CI, 0.68–1.09]), whereas NOAC s were associated with significantly higher dementia rates (2.16 events/100 person‐years versus 1.70 events/100 person‐years; weighted hazard ratio , 1.31 [95% CI, 1.07–1.59]) in patients 80 years and older. Conclusions This nationwide cohort of patients with atrial fibrillation revealed no clinically meaningful difference in dementia development between users of NOACs or warfarin apart from a higher risk in NOAC users 80 years and older, which may relate to residual confounding from selective prescribing and unobserved comorbidities.

Oral anticoagulant and reduced risk of dementia in patients with atrial fibrillation: A population-based cohort study

“…30 Nevertheless, data from a Danish population demonstrated no significant different in dementia development between DOAC and warfarin users, apart from those 80 years and older. 31 Therefore, considering our study results in the context of currently available evidence, we highlight the need for future studies with longer follow-up time and large sample sizes to understand DOAC treatment effects on dementia compared to warfarin. At present, there are two ongoing RCTs that focus on the impact of DOACs and warfarin on neurocognitive decline (ClinicalTrials.gov Identifier: NCT01994265 and NCT03061006).…”

The 2020 Canadian Cardiovascular Society/Canadian Heart Rhythm Society Comprehensive Guidelines for the Management of Atrial Fibrillation

“…499,500 Data relating to the DOACs and dementia are sparse, with some studies showing relative benefit compared with VKAs, 491,501,502 whereas a nationwide Danish cohort study did not. 503 Several clinical trials are being undertaken to allow greater clarity. In 2 of these studies, VKAs are being compared with dabigatran There are currently only 2 observational studies on the association between catheter ablation and cognitive dysfunction.…”

Prevention of Dementia in Patients with Atrial Fibrillation

“… 21) 22) In contrast, nationwide Swedish and Danish cohort studies found similar incidences of dementia when comparing warfarin and NOAC usage in their patients. 14) 23) Large longitudinal studies with a longer follow-up time are needed to clarify the effect of NOACs on cognitive functions. Currently, several randomized-controlled clinical trials focusing on cognitive outcomes in patients with AF are in progress.…”