Ablation therapies for paroxysmal atrial fibrillation: a systematic review and patient-level network meta-analysis

Abstract

Abstract Background Despite numerous promising trials, catheter ablation is still regarded as a second-line alternative to antiarrhythmic drugs (AAD) in the treatment of paroxysmal atrial fibrillation (PAF). There remains a role for a broad comparison of the effectiveness of various ablation therapies against each other, and versus AAD. Purpose To conduct a systematic review and network meta-analysis of ablation therapies and AAD in the treatment of PAF. Ablation therapies were hypothesized to be superior to AAD in preventing atrial fibrillation (AF) recurrence. Methods An electronic literature search was conducted to retrieve randomized controlled trials or propensity score-matched studies comparing freedom from AF recurrence among any combination of ablation modalities or AAD. Kaplan-Meier curves and risk tables for this outcome were graphically reconstructed to extract individual patient data (IPD). A Frequentist network meta-analysis (NMA) was performed using the derived hazard ratios (HRs) of each study to compare various ablation therapies and AAD. Two separate NMAs were also conducted with restricted mean survival time (RMST) analysis, using RMST absolute differences and ratios, in light of violation of the proportional-hazards assumption. Treatment strategies were ranked using P-scores. Pairwise comparisons were also performed between treatment pairs with three or more studies reporting direct comparisons. Results Across 24 studies comparing six ablation therapies, comprising 5274 patients, Frequentist NMA-derived HRs of AF recurrence compared to AAD were 0.35 (95% CI: 0.26–0.48) for cryoballoon ablation (CBA), 0.33 (95% CI: 0.25–0.45) for radiofrequency ablation (RFA), 0.21 (95% CI: 0.09–0.49) for combined CBA and RFA, 0.20 (95% CI: 0.11–0.39) for hot-balloon ablation (HBA), 0.44 (95% CI: 0.16–1.22) for laser-balloon ablation, and 0.33 (95% CI: 0.19–0.56) for pulmonary vein ablation catheter. RMST-based NMAs similarly showed a significant benefit of all ablation therapies over AAD in preventing AF recurrence. Although none of the HRs between pairs of ablation modalities were significant, P-scores for HBA and combined CBA and RFA were consistently higher than those of other treatments. Independent pairwise comparisons of RFA and CBA versus AAD were greatly in favor of ablation (shared-frailty HR=0.24, 95% CI: 0.19–0.31, p<0.001; shared-frailty HR=0.44, 95% CI: 0.35–0.56, p<0.001, respectively). Conclusions To our knowledge, this is the first network meta-analysis comparing a wide range of ablation therapies to AAD, synthesizing IPD from high-quality studies in three separate NMA models. The advantage of ablation therapies over AAD in preventing AF recurrence was consistently found across all three models. This strongly suggests that ablation should replace AAD as the first-line treatment for PAF in patients who are fit for the procedure. Moreover, the promising results of HBA underscore the need for more high-quality trials to be conducted. Funding Acknowledgement Type of funding sources: None.