BOSTON – Results from the CABANA trial, the long-awaited, head-to-head comparison of percutaneous catheter ablation with drug therapy for the treatment of atrial fibrillation by restoring sinus rhythm, failed to accomplish what it was designed to prove.
That is, that catheter ablation was superior to medical management for a combined endpoint of all-cause death, stroke, serious bleeding, or cardiac arrest.
Mitchel L. Zoler/MDedge News
Dr. Douglas L. Packer
The trial results also gave proponents of catheter ablation some tantalizing hints that this approach actually may have been superior to antiarrhythmic drugs, if only the randomization assignments had been more closely followed as the trial proceeded. But that didn’t happen, with about 30% of patients assigned to medical management crossing over to undergo catheter ablation, presumably because they had received inadequate symptom relief from their drug regimens. In addition, 10% of patients assigned to catheter ablation didn’t undergo it, primarily because they reconsidered after randomization and decided to not choose the invasive option. These crossovers produced a disparity in the outcomes between the standard, intention-to-treat analysis, which showed a neutral difference between the two study arms, and the per-protocol analysis that censored out crossover patients. The per-protocol analysis showed a statistically significant, 27% relative risk reduction in the primary endpoint among the patients randomized to and actually treated with catheter ablation, compared with those randomized to and exclusively treated medically.
“A patient can’t receive benefit from ablation if you don’t ablate,” noted the study’s lead investigation, Douglas L. Packer, MD, as he reported the results at the annual scientific sessions of the Heart Rhythm Society. “When you have this many crossovers and so many patients not getting their assigned treatments, then an on-treatment analysis is required, said Dr. Packer, a cardiac electrophysiologist and professor of medicine at the Mayo Clinic in Rochester, Minn.
The prespecified on-treatment analysis, which, instead of censoring crossover patients, analyzed outcomes based on the treatments that patients actually received, showed a statistically significant one-third reduction in the primary endpoint among the ablated patients and a statistically significant 40% relative reduction in all-cause mortality in the ablated arm, compared with those on medical management.
“For symptomatic treatment, and to restore and maintain sinus rhythm, there is no question that ablation is better. We knew that before this trial, and we know it even more convincingly now,” commented Jeremy N. Ruskin, MD, professor of medicine at Harvard Medical School and director of the cardiac arrhythmia service at Massachusetts General Hospital, both in Boston. “To a large extent, we do ablations for symptomatic benefit; to get patients feeling better. And I think this trial will confirm that because this will likely follow the better reduction in atrial fibrillation burden, which was quite impressive in the study.” Dr. Packer said that the quality of life data collected in CABANA will come out in a report later in 2018.