There was no advantage to catheter ablation for rhythm control in atrial fibrillation (AF) compared with an aggressive rate-control strategy in patients who also had heart failure (HF) in a randomized trial that was halted early and underpowered for the results to be conclusive.
But some trends suggested to researchers that, had there been continued enrollment and follow-up, the rhythm control strategy would have emerged as clearly superior, especially in at least one subgroup of patients.
In RAFT-AF, with a final enrollment of 363 out of a planned 600 patients with HF and a high burden of paroxysmal or persistent AF, those assigned to the ablation-based rhythm-control strategy showed a 23.4% rate of the primary endpoint of death or HF events over a median of about 3 years.
That compared to 32.5% for patients managed with rate control, which featured atrioventricular (AV) node-blocking meds supplemented, as needed, by AV node ablation followed by insertion of a biventricular pacemaker, the so called “ablate and pace” approach.
The hazard ratio (HR) for the primary endpoint was 0.71 (95% CI, 0.49 – 1.03, P = .066), favoring rhythm control.
Still, enrollment to RAFT-AF, which started in 2011, was halted in 2018 on its data-monitoring board’s recommendation because of “perceived futility” after what had been a follow-up averaging less than 20 months, said principal investigator Anthony S. Tang, MD, Western University, London, Ontario, Canada, when presenting the trial during the online American College of Cardiology (ACC) 2021 Scientific Sessions.
Of note, patients who entered the study with a left-ventricular ejection fraction (LVEF) no higher than 45% displayed what was considered a signal of possible benefit from the rhythm-control strategy vs rate control, a 37% reduction in risk of death or HF events (P = .059), Tang said. The risk-reduction came in at only 12% (P = .67) for patients with an LVEF greater than 45%.
“One interpretation of the results is that there is no difference between the two study groups on mortality and heart failure events. An alternate interpretation is that there is a benefit, but we had fewer patients enrolled in the study than initially planned,” Tang said, such that the difference failed to reach significance.
“We need to wait to see, sometimes, the benefit of maintaining sinus rhythm,” observed Christine M. Albert, MD, MPH, Cedars Sinai Medical Center, Los Angeles, California, as the invited discussant following Tang’s presentation. That should be kept in mind, she said, when planning target enrollments and necessary follow-up times in the design of clinical trials like RAFT-AF.
Had enrollment been allowed to continue as planned, Albert said that “probably you would have had a positive study. We don’t know that for sure, but I think we have to keep that in consideration when we interpret these findings.”
Tang said the two strategies were comparable with respect to serious adverse events, which occurred in about 50% of both the rhythm-control patients and rate-control patients. But the types of such events varied between the groups. For example, serious adverse events related to a catheter procedure — performed far less often in the rate-control group, who saw almost no such complications — reached 10.8% for patients managed with rhythm control. They included myocardial perforation or injury to the esophagus or pericardium in 4.2%.
“These patients oftentimes have a significant arrhythmia burden, they’re relatively frail, they’re older, and they have all these other associated things that increases the morbidity profile,” said Dhanunjaya R. Lakkireddy, MD, HCA Midwest Health, Overland Park, Kansas, putting the adverse-event rates in context.
“That being said, the trade-off I think is still worth it,” because the groups’ cumulative complication rates “are really not that much off,” Lakkireddy, not associated with RAFT-AF, told theheart.org | Medscape Cardiology.
The trial’s overall outcome is certainly not conclusive, “but I think it still is useful to help individual physicians determine treatment strategies. I would be less inclined to use the rhythm-control strategy for heart failure with preserved ejection fraction and more likely to use it in people with reduced ejection fraction,” said Tang in a statement to journalists covering the ACC sessions.
This story will soon be updated with further data and commentary.
RAFT-AF was funded by the Canadian Institutes of Health Research. Tang discloses receiving research support from Medtronic and Abbott.
American College of Cardiology 2021 Scientific Sessions: Abstract 411-12. Late-Breaking Clinical Trials — A Randomized Ablation-based Atrial Fibrillation Rhythm Control Versus Rate Control Trial In Patients With Heart Failure And High Burden Atrial Fibrillation (RAFT-AF)