Catheter ablation for atrial fibrillation leads to a reduction in atrial fibrillation, better quality of life and lower hospitalisations than medical therapy, but does not significantly reduce the risk of death, disabling stroke, serious bleeding, or cardiac arrest the CABANA (Catheter Ablation Versus Antiarrhythmic Drug Therapy for Atrial Fibrillation) trial has found.
The findings from the comparison of catheter ablation with medical therapy in atrial fibrillation were published in JAMA, and assessed the impact on cardiovascular events and mortality. A sub-study investigated improvements in quality of life.
Lead investigator Douglas Packer (Mayo Clinic, Rochester, MN, USA) describes the findings of reduced atrial fibrillation as “important”. Writing in JAMA, Packer et al say: “Among patients with atrial fibrillation, the strategy of catheter ablation, compared with medical therapy, did not significantly reduce the primary composite endpoint of death, disabling stroke, serious bleeding, or cardiac arrest. However, the estimated treatment effect of catheter ablation was affected by lower-than-expected event rates and treatment crossovers, which should be considered in interpreting the results of the trial.”
CABANA was an investigator-initiated, open-label, multicentre, randomised trial in 126 centres in 10 countries of 2,204 symptomatic patients with atrial fibrillation aged ≥65 years, or <65 years with ≥one risk factors for stroke. The catheter ablation group (n = 1108) underwent pulmonary vein isolation, and the drug therapy group (n = 1096) received standard rhythm and/or rate control drugs, according to guidelines.
Median age of participants was 68 years, and 37.2% were female; 42.9% had paroxysmal and 57.1% had persistent atrial fibrillation. In all, 90.8% (1006) of those assigned to catheter ablation underwent the procedure, and of those patients randomised to drug therapy, 301 (27.5%) ultimately received catheter ablation.
The primary endpoint for the analysis of mortality and cardiovascular events was a composite of death, disabling stroke, serious bleeding, or cardiac arrest. Three of the 13 pre-specified secondary endpoints were reported—all-cause mortality, total mortality or cardiovascular hospitalisation, and recurrence of atrial fibrillation.
In the intention-to-treat analysis, which had a median follow-up of 48.5 months, the primary endpoint occurred in 8% (n = 89) of patients in the ablation group compared with 9.2% (n = 101) in the drug therapy group (hazard ratio [HR] 0.86, 95% confidence interval [CI] 0.65–1.15, p = 0.30). For secondary endpoints, the rate of all-cause mortality was 5.2% in the ablation group compared to 6.1% in the drug therapy group (HR 0.85, 95% CI 0.60–1.21, p= 0.38). Outcomes were 51.7% vs. 58.1% for death or cardiovascular hospitalisation in the ablation and medical therapy groups (HR 0.83, 95% CI 0.74–0.93, p= 0.001), and 49.9% vs. 69.5% for recurrence of atrial fibrillation (HR 0.52, 95% CI 0.45–0.60, p < 0.001), respectively.
Packer et al comment that improvements in the secondary endpoint of mortality or cardiovascular hospitalisation are consistent with previous findings from CASTLE-AF and other studies, and show that “ablation was associated with improved primary endpoint and mortality outcomes, providing that the ablation group patients actually received ablative therapy”. Packer explains to Cardiac Rhythm News: “When we examined the data according to the pre-specified treatment actually received, the ablation group had significantly lower rates of death, as well as the combination of death, disabling stroke, serious bleeding or cardiac arrest compared with patients who only received drug therapy. Similarly, by per-protocol analysis, ablation patients showed significantly fewer deaths or adverse events.”
The association of catheter ablation with a lower rate of recurrence of atrial fibrillation than drug therapy (50% vs. 69% at three years postblanking follow-up) is also consistent with previous trials. But, the investigators say: “The long-term follow-up from this trial also shows that for many patients with atrial fibrillation, ablation is not curative. Work is ongoing to understand whether risk factor management, with or without ablation, can reduce recurrence rates.”
And they point to the impact of crossovers and withdrawals in the trial, a combined effect that they say reduced the estimated treatment effect and the precision of the effect size estimates, as assessed by intention-to treat.
But, in the meantime, Packer et al conclude: “Decisions about use of catheter ablation in individual patients need to consider both relative and absolute treatment differences, as well as procedural risks. For many patients meeting the eligibility criteria of this trial, expected treatment differences on an absolute scale will likely not be of sufficient magnitude to support a recommendation for catheter ablation on that basis alone.”
In the sub-study, led by Daniel Mark (Duke University, North Carolina, USA), the co-primary endpoints were quality of life at 12 months as measured on the Atrial Fibrillation Effect on Quality of Life (AFEQT) summary score, and both the Mayo AF-Specific Symptom Inventory (MAFSI) frequency and severity scores. At one year, mean scores for all three measures were more favourable in the catheter ablation group than the drug therapy group (Atrial Fibrillation Effect on Quality of Life summary score 86.4 points vs. 80.9 points, 95% CI 3.7–6.9, p < 0.001).
Mark and his co-investigators point out that, although interpretation of quality of life data can be challenging, because both of the co-primary endpoints in the study showed a mean treatment effect size for ablation that was equal to the patient-level benchmark it implies “that a substantial proportion of patients had sizable, clinically important incremental improvements after catheter ablation relative to drug therapy”, which can “help guide decisions regarding management of atrial fibrillation”.