The CABANA trial showed that ablation is not superior to drug therapy for CV outcomes at 5 years among patients with new-onset or untreated atrial fibrillation (AF) that required therapy.

Description

The goal of the trial was to compare the safety and efficacy of catheter ablation compared with drug therapy for the treatment of patients with new-onset or untreated AF.

Study design

Patients were randomized in a 1:1 fashion to either catheter ablation (n = 1,108) or drug therapy (n = 1,096). Primary ablation was performed with standard techniques (pulmonary vein isolation [PVI]/wide area circumferential ablation [WACA], ancillary ablations as needed). Drug therapy could be either for rate or rhythm control. All patients received anticoagulation.

•Total number of enrollees: 2,204
•Duration of follow-up: 5 years
•Mean patient age: 67.5 years
•Percentage female: 37%

Inclusion criteria:

•Paroxysmal, persistent, or longstanding persistent AF patients who warrant therapy
•≥65 years of age
•<65 years of age with ≥1 cerebrovascular accident (CVA)/cardiovascular (CV) risk factor
•Eligible for ablation
•On ≥2 rhythm or rate control drugs

Other salient features/characteristics:

•Cardiomyopathy: 9%
•Chronic heart failure: 15%
•Prior CVA/transient ischemic attack (TIA): 10%
•Type of AF—paroxysmal: 43%, persistent: 47%
•Prior hospitalization for AF: 39%
•Crossover—ablation to drug: 9.2%, drug to ablation: 27.5%

Principal findings

The primary outcome, death, disabling stroke, serious bleeding, or cardiac arrest at 5 years for ablation vs drug therapy, was 8% vs 9.2% (hazard ratio [HR] 0.86, 95% confidence interval [CI] 0.65-1.15, p = 0.3):

•Death: 5.2% vs 6.1% for ablation vs drug therapy, p = 0.38
•Serious stroke: 0.3% vs 0.6% for ablation vs drug therapy, p = 0.19
•Primary endpoint based on treatment received (for ablation vs drug therapy): 7.0% vs 10.9%, p = 0.006; all-cause mortality: 4.4% vs 7.5%, p = 0.005; death or CV hospitalization: 41.2% vs 74.9%, p = 0.002

Secondary outcomes:

•Death or CV hospitalization: 51.7% vs 58.1% for ablation vs drug therapy, HR 0.83, 95% CI 0.74-0.93, p = 0.002
•Time to first AF recurrence: HR 0.53, 95% CI 0.46-0.61, p < 0.0001
•Pericardial effusion with ablation: 3.0%; ablation-related events: 1.8%

Interpretation

The results of this important trial indicate that ablation is not superior to drug therapy for CV outcomes at 5 years among patients with new-onset or untreated AF that required therapy. There was a significant reduction in death or CV hospitalization with ablation, and on as-treated analysis, ablation demonstrated superior efficacy to drug therapy. In the setting of a negative primary endpoint, the latter two findings are considered hypothesis generating.

A couple of caveats exist. The drug-therapy arm is very heterogeneous, and it is unclear if uniform pursuance of rhythm control in that arm would be better than the rate control arm. The included population is also somewhat unclear with respect to the patients who would most benefit with this therapy.

Finally, this trial is only single-blinded (not to intervention received). That may have driven the high crossover rates and can confound assessment of the various endpoints. Based on recent experiences from important sham-controlled trials (eg, SYMPLICITY), these findings should prompt consideration of a sham-controlled trial to assess the true efficacy of catheter ablation in modulating CV outcomes among patients with AF.