Statins May Lower Dementia Risk in Patients With AF on Oral Anticoagulants

Oral anticoagulant therapy in patients with nonvalvular atrial fibrillation receiving statin therapy can decease risk for dementia.

In patients with nonvalvular atrial fibrillation (NVAF) who receive oral anticoagulants (OAC), use of statin therapy lowers dementia risk, according to a study in the European Heart Journal: Cardiovascular Pharmacotherapy.

Investigators compared the risk for dementia between users and nonusers of statins in patients with NVAF receiving OAC from the Korean National Health Insurance Service database from January 2013 to December 2017.

Diagnoses were based on the International Classification of Diseases, 10th Revision, Clinical Modification, and eligible participants had a CHA2DS2-VASc score of 2 or higher.

The primary endpoint was the occurrence of dementia. The risk for events was assessed with use of Cox proportional hazards analysis, and cumulative incidences of clinical endpoints were developed as Kaplan–Meier estimates based on therapy used and were compared with the log-rank test.

The cohort included 91,018 patients with NVAF, 17,700 patients in the statin therapy group and 73,318 patients in the nonstatin therapy group. The statin therapy group was older (mean age, 69.3 vs 67.9 years, P <.001) and had a lower percentage of women (45.6% vs 47.1%, P <.001).

Statin therapy was associated with a dose-dependent reduction in dementia in these patients.

Patients in the statin group had a higher CHA2DS2-VASc score (4.3±1.5) compared with the nonstatin group (4.1±1.3). The statin group also had a higher prevalence of hypertension, diabetes mellitus, dyslipidemia, myocardial infarction, and peripheral artery disease, compared with the nonstatin group. The median follow-up was similar in the statin therapy group (2.14 years) and the nonstatin therapy group (2.10 years; P =.132).

Warfarin or non-vitamin K antagonist oral anticoagulant therapy alone was associated with a significantly reduced risk for dementia vs non-OAC therapy (hazard ratio [HR], 0.74; 95% CI, 0.62-0.85; and HR, 0.62; 95% CI, 0.51-0.73, respectively) in patients with NVAF. Risk for dementia was significantly lower in the statin group (HR, 0.77; 95% CI, 0.64-0.90). Low-, moderate-, and high-intensity statin use was associated with a decreased risk for dementia vs nonstatin therapy (HR, 0.81; 95% CI, 0.69-0.94; HR, 0.74; 95% CI, 0.61-0.88; and HR, 0.67; 95% CI, 0.55-0.80, respectively; P for trend =.001).

Dementia incidence in the nonstatin group was significantly higher vs the statin group in patients who had CHA2DS2-VASc scores of 2 or 3 and 4 or higher (log-rank P <.001 for both).

Limitations of the study include the nonrandomized, retrospective, observational design. Additionally, the drug adherence rate was not measured owing to the inherent limitations of the claims data, and the investigators could not assess the effects of the different types of statins and off-label, underdosed, or different types of direct-acting oral anticoagulants.

“Statin therapy was associated with a dose-dependent reduction in dementia in these patients,” wrote the study authors. “Prospective randomized trials with an adequate follow-up period are warranted to explore whether this relationship is causal.”


Kim MH, Yuan SL, Lee KM, et al. Statin therapy reduces dementia risk in atrial fibrillation patients receiving oral anticoagulants. Eur Heart J Cardiovasc Pharmacother. Published online June 8, 2023. doi: 10.1093/ehjcvp/pvad039