In HF, AF, rhythm control with ablation not superior to rate control; trial underpowered
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Ablation-based rhythm control for patients with HF and atrial fibrillation did not significantly reduce all-cause death and HF events compared with a rate-control strategy, a speaker reported.
Patients in the ablation-based rhythm control group had fewer events and experienced marked improvements in left ventricular ejection fraction, quality of life and N-terminal pro B-type natriuretic peptide compared with the rate control group; however, the study size was too small to be definitive.
“In this trial of patients with atrial fibrillation and heart failure, the reduction of all-cause mortality and heart failure events with ablation-based rhythm control did not reach statistical significance as compared to rate control,” Anthony S.L. Tang, MD, cardiologist and professor of medicine at Western University in London, Canada, said during the presentation of RAFT-AF at the virtual American College of Cardiology Scientific Session. “Patients in the ablation-based rhythm control group had numerically fewer primary outcome events and had greater improvement of LV function, improvement in quality of life and reduction of NT-proBNP than patients in the rate control group. There was no difference in the number of patients who had serious adverse events in the two study groups.”
For this analysis, researchers enrolled 411 patients with HF and AF and randomly assigned to receive ablation-based rhythm control or medical therapy-based rate control.
The rhythm control group received pulmonary vein isolation with or without ablation of additional lesions. The rate control group received drugs or atrioventricular node modification and biventricular pacing to achieve a heart rate of 80 bpm or less while at rest and 110 bpm or less during a 6-minute walk test.
Researchers hypothesized that rhythm control would reduce the primary outcome of mortality and HF events among patients with HF with reduced or preserved EF compared with rate control.
Recruitment was stopped in January 2018 after the interim analysis due to lower-than-expected enrollment rate; lower-than-expected event rate; and perceived futility based on the data of 363 patients followed for a median of 19.5 months (futility index = 0.81).
At 5-year follow-up, reduction of the incidence of the primary outcome with ablation-based rhythm control did not achieve statistical significance compared with rate control (HR = 0.71; 95% CI, 0.49-1.03; P = .066).
Although ablation-based rhythm control did not reach statistical significance for the primary outcome, the proportion of patients who experienced all-cause mortality and HF events was lower in the rhythm control group compared with the rate control group.
“The study didn’t have a sufficient sample size to be definitive, but it is highly suggestive that ablation-based rhythm control appears to reduce the primary outcome measures, along with secondary outcomes of quality of life and heart failure markers, in patients who have heart failure with reduced ejection fraction,” Tang said in a press release. “It’s not quite as conclusive as I’d like it to be, 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.”
When participants were stratified by LVEF, those with LVEF greater than 45% trended toward better 5-year survival with rhythm control vs. rate control (HR = 0.88; 95% CI, 0.48-1.61; P = .67) compared with patients with LVEF of 45% or less (HR = 0.63; 95% CI, 0.39-1.02; P = .059); however, this finding also failed to meet statistical significance.
Patients in the ablation-based rhythm control group also improved compared with the rate control group in the following:
- LVEF (P = .017);
- AF effect on quality of life questionnaire (P = .0005);
- Minnesota living with HF questionnaire (P = .0036);
- 6-minute walk distance (P = .025); and
- N-terminal pro-B natriuretic peptide levels (P = .025).
“One interpretation of results is that there is no difference between the two study groups on mortality and heart failure events,” Tang said during the presentation. “An alternate interpretation is that there is a benefit; however, we have fewer patients enrolled in the study than initially planned. In addition, there’s a time delay between treatment taking effect on mortality and heart failure events, and there appears to be a differential effect of ablation-based rhythm control over rate control between patients with LVEF less than or equal to 45% and those greater than 45%.”
Perspective
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Christine Albert, MD, MPH, FHRS
A major take home message from this research is that the benefits of ablation, and maintenance of sinus rhythm, in patients with AF may take some time to become apparent. This requires trial designs that build in longer durations of follow-up for both interim and final analyses. The enrollment in the trial was stopped early, and thus it was underpowered to detect the prespecified difference in the primary endpoint. However, the curves separated at the end of the trial, and the authors will be performing an extended follow-up. While the trial itself did not find a statistically significant difference in the primary endpoint, there was a benefit of ablation vs. rate control on intermediate endpoints, such as LVEF and NT-proBNP levels, as well as quality of life.
In the future, we should aim to have studies that can help identify which patients with HF benefit most from ablation. We have a lot of data that certain subgroups of patients with HF do benefit from ablation, and how we select those patients is not completely straightforward. As we saw in this study, the benefit seems to be more so in those with lower LVEF; however, data from the CABANA trial suggest there may be benefits even in patients who have HFpEF. It would be helpful to have more observational research to understand these nuances better before designing the next clinical trial.
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Tang A, et al. Late-Breaking Clinical Trials V. Presented at: American College of Cardiology Scientific Session; May 15-17, 2021 (virtual meeting).
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