Evaluation of the Risk of Stroke Without Anticoagulation Therapy in Men and Women With Atrial Fibrillation Aged 66 to 74 Years Without Other CHA2DS2-VASc Factors

Abstract

Importance: There are limited clinical trial data and discrepant recommendations regarding use of anticoagulation therapy in patients with atrial fibrillation (AF) aged 65 to 74 years without other stroke risk factors.

Objectives: To evaluate the risk of stroke without anticoagulation therapy in men and women with AF aged 66 to 74 years without other CHA2DS2-VASc (congestive heart failure, hypertension, age ≥75 years, diabetes, stroke, vascular disease, age 65-74 years, female sex) risk factors and examine the association of stroke incidence with patient age.

Design, setting, and participants: A population-based retrospective cohort study was conducted using linked administrative databases. The population included 16 351 individuals aged 66 to 74 years who were newly diagnosed with AF in Ontario, Canada, between April 1, 2007, and March 31, 2017. Exclusion criteria included long-term care residence, prior anticoagulation therapy, valvular disease, heart failure, hypertension, diabetes, stroke, and vascular disease. The cumulative incidence function was used to estimate the 1-year incidence of stroke in patients who did not receive anticoagulation therapy. Fine-Gray regression was used to study the association of patient characteristics with stroke incidence and derive estimates of stroke risk at each age. Death was treated as a competing risk and patients were censored if they initiated anticoagulation therapy. Inverse probability of censoring weights was used to account for patient censoring. Data analysis was performed from May 26, 2019, to December 9, 2020.

Exposures: Atrial fibrillation and age.

Main outcomes and measures: Hospitalizations for stroke.

Results: Of the 16 351 individuals with AF (median [interquartile range] age, 70 [68-72] years), 8352 (51.1%) were men; 6314 individuals (38.6%) started anticoagulation therapy during follow-up. The overall 1-year stroke incidence among patients who did not receive anticoagulation therapy was 1.1% (95% CI, 1.0%-1.3%) and the incidence of death without stroke was 8.1% (95% CI, 7.7%-8.5%). The incidence of stroke was not significantly associated with sex. The estimated 1-year stroke risk increased with patient age from 66 years (0.7%; 95% CI, 0.5%-0.9%) to 74 years (1.7%; 95% CI, 1.3%-2.1%).

Conclusions and relevance: The risk of stroke more than doubled in this study as men and women with AF but no other CHA2DS2-VASc risk factors aged from 66 to 74 years. These data suggest that anticoagulation therapy is more likely to benefit older individuals within this group of patients, whereas younger individuals are less likely to gain net clinical benefit from anticoagulation therapy.

Figure 1.. Risk of Hospitalization for Stroke in Patients With Newly Diagnosed Atrial Fibrillation Not Receiving Anticoagulation Therapy

Patients were censored when they started anticoagulation therapy and death was treated as a competing risk. Patient data were weighted by the inverse probability of censoring.

Figure 2.. Predicted 1-Year Incidence of Stroke at Each Age Between 66 and 74 Years Among Nonanticoagulated Patients Not Receiving Anticoagulation Therapy

Death was treated as a competing risk. Patients were censored when they started anticoagulation and were weighted by the inverse of the probability of censoring. Error bars indicate 95% CI. The dotted line indicates 1-year stroke incidence in the full cohort (1.1%).