Medical Therapy, Radiofrequency Ablation, or Cryoballoon Ablation as First-Line Treatment for Paroxysmal Atrial Fibrillation: Interpreting Efficacy Through the Shiny Method

Abstract

In patients with paroxysmal atrial fibrillation, cryoballoon ablation (CBA) and radiofrequency ablation (RFA) represent two therapeutic approaches supported by increasing literature. While both these ablation techniques play a role during different stages of the patient’s therapeutic pathway, their use as first-line is being increasingly recognized. This scoping review comparatively examined the evidence of effectiveness for these two ablation techniques. Our analysis was limited to the evaluation of the end-point of time to recurrence of atrial fibrillation (or other forms of atrial arrhythmias), which was the primary end-point in most clinical trials. The method used for pooling the information from clinical trials (Shiny method) is original and based on an artificial intelligence (AI) method that reconstructs individual patient data from published Kaplan-Meier time-to-event curves. Because a network meta-analysis has been published on this same clinical material, one objective of the present work was to compare the meta-analytic results with those generated by the Shiny method. A standard literature search was conducted on PubMed/Medline. Only randomized studies comparing CBA versus medical therapy, RFA versus medical therapy, or CBA versus RFA in previously untreated patients were eligible. Trials presenting a Kaplan-Meier curve to present the above-mentioned end-point were included. Patient-level data were reconstructed by application of the Shiny method. These individual patient data were then analyzed by standard statistical testing based on hazard ratio (HR) for risk of recurrence and medians of time to recurrence. Our analysis compared the two ablation treatments and medical therapy. A total of five trials were identified through our literature search. Information from these trials was pooled according to the three treatments (CBA: three trials, n = 365; RFA: two trials, n = 99; medical therapy: five trials, n = 457). CBA showed higher effectiveness than medical therapy (HR, 0.51; 95% confidence interval (CI): 0.38 to 0.67). In comparison with medical therapy, RFA showed a numerical trend that remained far from statistical significance (HR, 0.89; 95% CI: 0.62 to 1.27). Medians for time to recurrence were 14.1 months (95% CI: 10.0 to not reached) for RFA and 11.5 months (95% CI: 9.3 to 25.3) for medical therapy. This parameter was not reached for CBA. The current evidence from five randomized trials suggests that CBA ranks first in effectiveness, followed by RFA and medical therapy. In our comparison between the results generated by the Shiny method with those published in the previous meta-analysis, the Shiny method confirmed its ability to account for the length of follow-up in individual trials, whereas the meta-analytic approach confirmed its ability to account for the effects of randomizations performed in the trials.

Frozen Hearts: The Emerging Role of Cryoablation for Pulmonary Vein Isolation

“…RMT has been associated with reduced operative morbidity and decreased intensive care unit stays. Major surgical complications were also found to be significantly lower in the RMT groups in composition to standard surgical approach [39].…”

Survival in Patients with Relapsed-Refractory Multiple Myeloma: Indirect Comparison of Six New Treatments

“…The main, well known limitation of the Shiny method is that this approach does not allow one to perform any multivariate analyses [ 18 , 19 ]. In more detail, while the covariate represented by the treatment can be adequately analyzed, no other variables beyond the treatment can generally be evaluated.…”

“…One strength of our analysis is the excellent performance of the Shiny method in reconstructing individual patient data from published Kaplan-Meier survival curves [10,[13][14][15][16]. Its main weakness lies in the indirect nature of our comparisons, with all consequent implications already discussed in previous studies [18,19].…”

Survival in Patients With Relapsed-Refractory Multiple Myeloma: Indirect Comparison of Six New Treatments

“…The main, well-known limitation of the Shiny method is that this approach does not allow to perform any multivariate analyses [19]. In more detail, while the covariate represented by the treatment can be adequately analyzed, no other variables beyond the treatment can generally be evaluated.…”

“…One strength of our analysis is the excellent performance of the Shiny method in reconstructing individual patient data from published Kaplan-Meier survival curves [10,[13][14][15][16][17]. Its main weakness lies in the indirect nature of our comparisons with all consequent implications already discussed in previous studies [19]. Patients had received at least two prior lines of therapy, including an immunomodulatory agent and proteasome inhibitor, and were refractory to pomalidomide and/or an anti-CD38 monoclonal antibody.…”