(P-585) Association Between Oral Anticoagulants and Risk of Dementia in Patients with Non-valvular Atrial Fibrillation

Background: Non-valvular atrial fibrillation (NVAF) is associated with an increased risk of dementia. Oral anticoagulants (OACs), such as warfarin and direct OACs, may prevent dementia in these patients and recent reviews have called for further research, given methodological limitations in previous observational studies.

Objectives: To assess whether the use of OACs is associated with the risk of dementia among patients with NVAF.

Methods: We used the Clinical Practice Research Datalink, a UK primary care database with over 15 million patients, to form a cohort of all patients aged 50 years or more, with an incident diagnosis of NVAF (cohort entry) between 1988 and 2017 and no prior OAC use, with follow-up until December 2019. Follow-up began 6 months after cohort entry for latency considerations. Patients were considered unexposed until six months after their first OAC prescription (six-month lag period) and exposed thereafter until the end of follow-up. We identified with a first diagnosis of dementia (any type) during follow-up. We used time-dependent Cox proportional hazards models to estimate adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) for dementia associated with OAC use, compared with no use. We assessed whether the risk varied with cumulative duration of OAC use, compared with no use, both by stratifying duration into three categories (≤ 2 years, 2-5 years, > 5 years) and by modelling the HR using a restricted cubic spline. We also assessed whether there was effect measure modification by age, sex, and ischemic stroke prior to NVAF diagnosis.

Results: The cohort included 142,227 NVAF patients, with 8,023 cases of dementia over a mean follow-up of 4.7 years, yielding an incidence rate of 12.1 (95% CI: 11.9-12.4) per 1,000 person-years. OAC use was associated with a decreased risk of dementia (HR: 0.90; 95% CI: 0.85-0.94), compared with no use. A decreased risk was observed with less than 2 years of cumulative duration of OAC use (HR: 0.90; 95% CI: 0.84-0.95), 2-5 years (HR: 0.87; 95% CI: 0.81-0.93), and > 5 years (HR: 0.88; 95% CI: 0.81-0.95), compared with no use. The spline suggested a decreased risk of dementia, reaching a low at approximately 1.5 years of cumulative OAC use and stabilizing thereafter. OAC use decreased the risk of dementia in patients aged ≥ 75 years (HR: 0.84; 95% CI: 0.80-0.89), but not in younger patients (HR: 0.99; 95% CI: 0.90-1.10). The risk did not vary by sex or previous ischemic stroke before NVAF diagnosis.

Conclusions: In patients with incident NVAF, the use of OACs was associated with a decreased risk of dementia, evident after 1-2 years of OAC use.