Generalizability of the CASTLE-AF trial: Catheter ablation for patients with atrial fibrillation and heart failure in routine practice

Background: In the Catheter Ablation for Atrial Fibrillation with Heart Failure (CASTLE-AF) trial, catheter ablation reduced the risk of death and heart failure (HF) hospitalization in patients with atrial fibrillation and HF by 40%. Objectives: The study aimed to assess the generalizability of CASTLE-AF to routine clinical practice. Methods: Using a large US administrative database, we identified 289,831 patients with atrial fibrillation and HF treated with ablation (n = 7465) or medical therapy alone (n = 282,366) from January 1, 2008, through August 31, 2018. Patients were divided into 3 groups on the basis of trial eligibility: (1) eligible for CASTLE-AF, (2) failing to meet the inclusion criteria, and (3) meeting at least 1 of the exclusion criteria. Propensity score overlap weighting was used to balance ablated and drug-treated patients on 90 baseline characteristics. Cox proportional hazards regression was used to compare ablation with medical therapy for the primary outcome of a composite end point of all-cause mortality and HF hospitalization. Results: Only 7.8% of patients would have been eligible for the trial; 91.0% failed to meet the trial inclusion criteria; and 15.5% met the exclusion criteria. Ablation was associated with a lower risk of the primary outcome in the overall cohort (hazard ratio [HR] 0.81; 95% confidence interval [CI] 0.76–0.87; P < .001), in the trial-eligible cohort (HR 0.82; 95% CI 0.70–0.96; P = .01), and in patients who failed to meet inclusion criteria (HR 0.79; 95% CI 0.73–0.86; P < .001) but not in patients who met the exclusion criteria (HR 0.97; 95% CI 0.81–1.17). The relative risk reduction was consistent regardless of whether patients had HF with reduced left ventricular ejection fraction. Conclusion: The benefit associated with ablation appears to be more modest in practice than that reported in the CASTLE-AF trial.