Background: In older patients with atrial fibrillation (AF), cognitive impairment and frailty are prevalent. It is unknown whether the risk and benefit of anticoagulation differ by cognitive function and frailty.

Methods: A total of 1244 individuals with AF with age ≥65 years and a CHADSVASC score ≥2 were recruited from clinics in Massachusetts and Georgia between 2016 and 18 and followed until 2020. At baseline, frailty status and cognitive function were assessed. Hazard ratios of anticoagulation on physician adjudicated outcomes were adjusted by the propensity for receiving anticoagulation and stratified by cognitive function and frailty status.

Results: The average age was 75.5 (± 7.1) years, 49% were women, and 86% were prescribed oral anticoagulants. At baseline, 528 (42.4%) participants were cognitively impaired and 172 (13.8%) were frail. The adjusted hazard ratios of anticoagulation for the composite of major bleeding or death were 2.23 (95% confidence interval: 1.08-4.61) among cognitively impaired individuals and 0.94 (95% confidence interval: 0.49-1.79) among cognitively intact individuals (P for interaction = 0.08). Adjusted hazard ratios for anticoagulation were 1.84 (95% confidence interval: 0.66-5.13) among frail individuals and 1.39 (95% confidence interval: 0.84-2.40) among not frail individuals (P for interaction = 0.67).

Conclusion: Compared with no anticoagulation, anticoagulation is associated with more major bleeding episodes and death in older patients with AF who are cognitively impaired.