No reduction in mortality and CV outcomes with catheter ablation in AF
Effect of Catheter Ablation vs Antiarrhythmic Drug Therapy on Mortality, Stroke, Bleeding, and Cardiac Arrest Among Patients With Atrial Fibrillation The CABANA Randomized Clinical TrialLiterature - Packer DL, Mark DB, Robb RA, et al. - JAMA 2019; doi:10.1001/jama.2019.0693
Introduction and methods
Catheter ablation for atrial fibrillation (AF) is nowadays a therapeutic option for a wide range of AF patients and several reports have suggested it is more effective in reducing recurrent AF events than antiarrhythmic drug therapy [1-5]. One small trial of ablation vs. drug therapy in symptomatic AF patients and systolic HF patients suggested that successful ablation may extend survival . However, data of large randomized clinical trials on outcomes with ablation vs. medical therapy are lacking.
Therefore, the investigator-initiated, multicenter, prospective, randomized, open-label Catheter Ablation vs Antiarrhythmic Drug Therapy for Atrial Fibrillation (CABANA) trial tested whether ablation for AF was more effective in reducing the primary outcome, a composite of death, disabling stroke, serious bleeding or cardiac arrest, compared to drug therapy in symptomatic and inadequately treated AF patients. The trial enrolled 2204 patients ≥65 years or <65 years with 1 or more risk factors for stroke, and who had 2 or more episodes of paroxysmal AF or 1 episode of persistent AF 6 months prior to randomization. From Nov 2009 to April 2016, patients were randomized in 1:1 ratio to catheter ablation (n=1108) or drug therapy (n=1096). Follow-up continued until Dec 2017, for a median duration of 48.5 months. Secondary end points were overall mortality, overall mortality or CV hospitalization, and AF recurrence.
Co-primary endpoint of quality of life (QoL) was determined at 12 months using the Atrial Fibrillation Effect on Quality of Life (AFEQT) summary score and the Mayo AF-Specific Symptom Inventory (MAFSI) frequency score and severity score (published by Mark DB, Anstrom KJ, Sheng S, Effect of Catheter Ablation vs Medical Therapy on Quality of Life Among Patients With Atrial Fibrillation -The CABANA Randomized Clinical Trial, JAMA 2019, doi: 10.1001/jama.2019.0692).
During the trial, the design was modified due to slow enrollment and lower than expected aggregated event rates (a mortality rate of 12% at 3 years was estimated, but actual mortality rate was 4.1% at 3 years). In Feb 2013, the key secondary endpoint, a composite of death, disabling stroke, serious bleeding, or cardiac arrest became the primary endpoint, all-cause mortality became the key secondary endpoint, and follow-up was extended to an average of 4 years or longer.
Of the 1008 patients assigned to catheter ablation, 1006 (90.8%) underwent ablation with 215 patients (19.4%) undergoing repeat procedures. In the catheter ablation group, 44.6% also received antiarrhythmic drugs at some point during the trial and 26.5% at the last follow-up. A total of 301 patients (27.5%) in the drug therapy group crossed over to catheter ablation during follow-up.
- In the intention-to-treat (ITT) analysis, the primary composite outcome occurred in 8.0% in the catheter ablation group and 9.2% in the drug therapy group (HR 0.86, 95%CI:0.65-1.15, log-rank P=0.30).
- In the ITT analysis, 5.2% in the catheter ablation group died and 6.1% in the drug therapy group (HR 0.85, 95%CI: 0.60-1.21, log-rank P=0.38). The endpoint of all-cause mortality or CV hospitalization occurred in 51.7% in the catheter ablation group and 58.1% in the drug therapy group (HR 0.83, 95%CI: 0.74-0.93, log-rank P=0.001).
- The secondary endpoint of AF recurrence (measured by study ECG event recording system in 1240 patients), analyzed by ITT with death as a competing risk, was reduced in the catheter ablation group vs. medical therapy group (adjHR 0.52, 95%CI: 0.45-0.60, P<0.001).
- In the treatment received analysis, the primary composite endpoint was reduced with catheter ablation vs. drug therapy (HR 0.67, 95%CI: 0.50-0.89, P=0.006). All-cause mortality and death or CV hospitalization were also reduced with catheter ablation vs. medical therapy (HR 0.60, 95%CI: 0.42-0.86, P=0.005, HR 0.83, 95%CI: 0.74-0.94, P=0.002, respectively).
- Most common serious adverse event in the catheter ablation group was cardiac tamponade (0.8%). Other adverse events in the catheter ablation group were minor hematomas (2.3%) and pseudoaneurysms (1.1%). In the drug therapy group, thyroid disorders (1.6%) and proarrhythmia (0.8%) were reported.
- At 12 months, mean summary AFEQT scores (rang 0-100, lower score means more AF-related disability) were 86.4 points in the catheter ablation group and 80.9 points in the drug therapy group (mean difference 5.3 points, 95%CI:3.7-6.9, P<0.001). Mean MAFSI frequency score (range 0-40, higher score means higher frequency) at 12 months was 6.4 points in the catheter ablation group and 8.1 points in the drug therapy group (mean difference -1.7 points, 95%CI:-2.3 to -1.2, P<0.001). Mean MAFSI severity score (range 0-30, lower score indicates less severe symptoms) was 5.0 points in the catheter ablation group vs. 6.5 points in the drug therapy group (difference -1.5 points, 95%CI:-2.0 to -1.1, P<0.001).
In symptomatic AF patients, catheter ablation did not reduce the primary outcome of death, disabling stroke, serious bleeding, and cardiac arrest compared to drug therapy. Treatment crossovers and lower than expected mortality rates may have affected the findings in this study. Analysis of QoL in the CABANA trial population showed an improvement in QoL with catheter ablation vs. medical therapy in AF patients after 12 months.