Association Between Age and Outcomes of Catheter Ablation Versus Medical Therapy for Atrial Fibrillation: Results From the CABANA Trial

Abstract

Background: Observational data suggest that catheter ablation may be safe and effective to treat younger and older patients with atrial fibrillation. No large, randomized trial has examined this issue. This report describes outcomes according to age at entry in the CABANA trial (Catheter Ablation versus Antiarrhythmic Drug Therapy for Atrial Fibrillation).

Methods: Patients with atrial fibrillation ≥65 years of age, or <65 with ≥1 risk factor for stroke, were randomly assigned to catheter ablation versus drug therapy. The primary outcome was a composite of death, disabling stroke, serious bleeding, or cardiac arrest. Secondary outcomes included all-cause mortality, the composite of mortality or cardiovascular hospitalization, and recurrence of atrial fibrillation. Treatment effect estimates were adjusted for baseline covariables using proportional hazards regression models.

Results: Of 2204 patients randomly assigned in CABANA, 766 (34.8%) were <65 years of age, 1130 (51.3%) were 65 to 74 years of age, and 308 (14.0%) were ≥75 years of age. Catheter ablation was associated with a 43% reduction in the primary outcome for patients <65 years of age (adjusted hazard ratio [aHR], 0.57 [95% CI, 0.30-1.09]), a 21% reduction for 65 to 74 years of age (aHR, 0.79 [95% CI, 0.54-1.16]), and an indeterminate effect for age ≥75 years of age (aHR, 1.39 [95% CI, 0.75-2.58]). Four-year event rates for ablation versus drug therapy across age groups, respectively, were 3.2% versus 7.8%, 7.8% versus 9.6%, and 14.8% versus 9.0%. For every 10-year increase in age, the primary outcome aHR increased (ie, less favorable to ablation) an average of 27% (interaction P value=0.215). A similar pattern was seen with all-cause mortality: for every 10-year increase in age, the aHR increased an average of 46% (interaction P value=0.111). Atrial fibrillation recurrence rates were lower with ablation than with drug therapy across age subgroups (aHR 0.47, 0.58, and 0.49, respectively). Treatment-related complications were infrequent for both arms (<3%) regardless of age.

Conclusions: We found age-based variations in clinical outcomes for catheter ablation compared with drug therapy, with the largest relative and absolute benefits of catheter ablation in younger patients. No prognostic benefits for ablation were seen in the oldest patients. No differences were found by age in treatment-related complications or in the relative effectiveness of catheter ablation in preventing recurrent atrial arrhythmias.

Registration: URL: https://www.

Clinicaltrials: gov; Unique identifier: NCT00911508.

Keywords: age groups; anti-arrhythmia agents; atrial fibrillation; catheter ablation; pulmonary veins.

Figure 1:

Treatment Effect on Primary Outcome as a Function of Age as a Continuous Variable. The relative risk reduction with catheter ablation vs drug therapy as a function of age as a continuous variable for the primary composite outcome of death, disabling stroke, serious bleeding, or cardiac arrest. The figure shows the adjusted hazard ratio as a solid black line with the 95% confidence intervals represented as the shaded area. The drug arm is used as reference group. aHR=adjusted hazard ratio, CI=confidence interval

Figure 2:

Four-Year Kaplan-Meier Event Rates and Unadjusted and Adjusted Hazard Ratios by Intention-to-Treat Age Subgroups. AF=atrial fibrillation, CI=confidence interval, CIF=cumulative incidence function, CV=cardiovascular, HR=hazard ratio, KM=Kaplan-Meier

Figure 3:

Treatment Effect on Total Mortality as a Function of Age as a Continuous Variable. The relative risk reduction with catheter ablation vs drug therapy as a function of age as a continuous variable for total mortality. The figure shows the adjusted hazard ratio as a solid black line with the 95% confidence intervals represented as the shaded area. The drug arm is used as reference group. aHR=adjusted hazard ratio, CI=confidence interval.