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

IMPORTANCEThere 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 CHA 2 DS 2 -VASc (congestive heart failure, hypertension, age Ն75 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 PARTICIPANTSA 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. RESULTSOf 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 RELEVANCEThe risk of stroke more than doubled in this study as men and women with AF but no other CHA 2 DS 2 -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.

New Oral Anticoagulants Versus Vitamin K Antagonists in Patients with Left-Sided Bioprosthetic Heart Valves and Atrial Fibrillation: A Systematic Review and Meta-Analysis

“…However, the cut-off scores for starting anticoagulation varies between guidelines, leading to con icts over the choice of starting anticoagulation in elder patients [6,31−33] . A recent population-based cohort study of 16 351 individuals found a 2.4-fold increased risk of stroke in patients aged 66 to 74 years with AF but no other CHA 2 DS 2 -VASc risk factors [34] . This nding also provides support for the need of subgroup analysis according to age and incorporating age into the selection of anticoagulants for AF combined with BHV.…”

Impact of time-varying exposure on estimated effects in observational studies using routinely collected data: protocol for a cross-sectional study

“…Time-varying exposure, including treatment discontinuing, switching and adding-on, are common in routine care 10–12. For instance, a retrospective cohort study included 16 351 patients with atrial fibrillation showed that 38.6% patients involved treatment switching during 1-year follow-up 13. Another study evaluated treatment patterns in patients with plaque psoriasis, and showed that among patients treated with ixekizumab, 57.7% patients discontinued treatment and 30.2% switched to alternative biologic over the 2-year follow-up 14…”

Competing Risks, Treatment Switching, and Informative Censoring

“…Most guidelines recommend oral anticoagulation therapy for a CHA 2 DS 2 -VASc score of 2. The recommendations are mixed for CHA 2 DS 2 -VASc score of 1 . The Canadian Cardiovascular Society Guidelines now recommend anticoagulation in all patients with atrial fibrillation aged 65 years or younger .…”

“…The article published in this issue of JAMA Cardiology by Abdel-Qadir and colleagues addresses this gap by evaluating a cohort of 16 351 individuals between the ages of 66 and 74 years (potentially low risk) who were newly diagnosed with atrial fibrillation and not initially receiving anticoagulants between April 2007 and March 2017 in Ontario, Canada. The study estimates that 1-year stroke risk without anticoagulation therapy increases with patient age from 0.7% (95% CI, 0.5%-0.9%) at age 66 years to 1.7% (95% CI, 1.3%-2.1%) at age 74 years, suggesting that, even within the age category of 66 to 74 years, older patients have more to gain from anticoagulation therapy with respect to stroke risk reduction.…”

“…The first statistical issue involved competing risk. The overall incidence of stroke was 1.1%, whereas the incidence of death without stroke was 8.1% . Failure to account for the competing risk of death would have resulted in the overestimation of stroke risk.…”