The CABANA trial has demonstrated that catheter ablation is not superior to medical therapy for cardiovascular (CV) outcomes at 5 years, among patients with new-onset or untreated atrial fibrillation (AF) that require therapy. This was presented by Douglas Packer (Mayo Clinic) at the annual meeting of the Heart Rhythm Society (HRS) 2018.
AF causes impaired quality of life and serious complications such as heart failure and stroke. Medications used in treating atrial fibrillation often have important risks and side effects. Therefore catheter ablation was considered an important treatment modality. Although ablation seemed a favorable option, there was no clear evidence to support its benefit over medical therapy.
The goal of the Catheter ABlation vs ANtiarrthymic Drug Therapy for Atrial Fibrillation (CABANA) trial was to compare the efficacy and safety of left atrial catheter ablation compared with drug therapy for the treatment of patients with new-onset or untreated AF.
Patients were randomized to either catheter ablation (n = 1,108) or drug therapy (n = 1,096) in a 1:1 ratio. Standard techniques were used for primary left atrial ablation (pulmonary vein isolation /wide area circumferential ablation). Drug therapy could either be for rate or rhythm control. 87.2% of patients received rhythm control therapy. Anticoagulation was administered to subjects in both groups.
The intention-to-treat (ITT) analysis, which was considered as the primary analysis, indicated there was no statistically significant difference between ablation and drug treatment at 5 year follow-up in primary composite outcomes including death, disabling stroke, serious bleeding and cardiac arrest (p = 0.30). With regards to the secondary outcomes, ablation reduced composite of death or CV hospitalization (p= 0.001) which was mainly driven by CV hospitalization. However, per protocol (PP) analysis demonstrated that ablation was superior as compared to drug therapy with a significant difference in both primary (p =0.006) and secondary outcomes (all-cause mortality, p= 0.005; death or CV hospitalization, p= 0.002).
These results have led to a great deal of debate and discussion. While the majority of electrophysiologists support PP analysis which has promising results in favor of catheter ablation, the ITT supporters believe that basic epidemiological principles should not be violated in order to preserve the randomization. Importantly, during the course of the trial, 9.2% of patients randomized to ablation did not undergo ablation while 27.5% of patients randomized to drug therapy ended up undergoing ablation. This high crossover rate made the ITT analysis less reliable.
Another important issue was the the heterogeneity in the drug therapy which included both rate and various rhythm control strategies. In addition, this trial was only single-blinded. These findings should be confirmed by a sham-controlled trial for the assessment of the true efficacy of catheter ablation in the improvement of CV outcomes.
The investigators conclude that catheter ablation is an acceptable treatment in a selected group of patients with atrial fibrillation. Subgroup analyses may demonstrate the groups of patients who benefit more from ablation.