Data on first recurrence, Afib burden from expanded analysis of CABANA trial

Catheter ablation effectively curtailed the recurrence of any atrial fibrillation (Afib) by nearly half, and symptomatic Afib by more than half, versus drug therapy over five years of follow-up, according to an expanded analysis of the CABANA trial.

In over 1,000 patients with Afib, those in the catheter ablation group saw a reduction in first recurrence of any symptomatic or asymptomatic Afib (hazard ratio 0.52, 95% CI 0.45-0.60, P<0.001) or first symptomatic-only Afib (HR 0.49, 95% CI 0.39-0.61, P< 0.001) over 60 months of follow-up, reported Jeanne E. Poole, MD, of the University of Washington Medical Center, Seattle, and co-authors.

Baseline Holter Afib burden in both treatment groups was 48%, they stated in the Journal of the American College of Cardiology.

And at 12 months, Afib burden in ablation patients averaged 6.3% versus 14.4% in the drug-therapy patients. Also, Afib burden was significantly less in the ablation patients versus drug-therapy patients across the 5-year follow-up (P<0.001). “These findings were not sensitive to the baseline pattern of AF,” the authors noted.

What makes the current report “unique” is the “presentation of baseline and then every 6-month Afib burden as assessed by 96-h Holter in a large patient cohort… The CABANA trial report on late Afib recurrence confirms the clear benefit of catheter ablation versus pharmacological therapy in preventing recurrent Afib in patients with symptomatic Afib, and is important in being one the largest prospective studies to report on the benefit of catheter ablation on Afib burden.” noted Francis E. Marchlinski, MD, of the Hospital of the University of Pennsylvania in Philadelphia, and co-authors in an editorial comment accompanying the study.

Marchlinski’s group pointed out that “reporting treatment outcome based on Afib burden comes with its own set of challenges,” emphasizing that “A 96-h Holter monitor done twice a year might identify frequent, short-lived Afib, but can miss a single prolonged episode of comparable total Afib burden.”

Also, many patients will have no Afib after ablation, so “burden results for the entire group will be skewed to reflect those good outcomes if patients with no Afib during follow-up are included in the overall burden assessment.”

Lastly, any Afib burden would need to be accompanied by data on improvements in symptoms and quality of life versus baseline in order to manage the “marked intrapatient variability in the relationship between symptoms and Afib burden,” Marchlinski and co-authors stated. The current study did not provide that data, but “we anticipate it will be forthcoming in other CABANA publications.”

The primary outcome of the original CABANA trial was a composite of death, disabling stroke, serious bleeding, or cardiac arrest. During a median follow up of 48.5 months, and by intention-to-treat (ITT) analysis, the primary results showed a14% reduction in the primary endpoint (HR 0.86; 95% CI 0.65-1.15; P=0.303) and a 15% reduction in the main secondary endpoint of all-cause mortality (HR 0.85, 95% CI 0.60-1.21, P=0.377).

Results from the original CABANA trial bolstered the use of catheter ablation as an effective treatment approach for a broad range of patients with Afib, and also set out to “define the long-term risk of Afib recurrence in patients treated with catheter ablation compared with drug therapy, both in terms of first recurrence, as well as the overall burden of Afib,” Poole’s group explained. “Initial results reported from the CABANA study showed a significant 48% reduction in recurrence of Afib with follow-up to 48 months.”

For the current expanded analysis of the CABANA ECG rhythm dataset, the authors prospectively studied patients with a proprietary ECG recording monitor for symptom-activated and 24-hour Afib auto detection. The Afib recurrence endpoint was any post-90-day blanking atrial tachyarrhythmias lasting ≥30 seconds. Biannual 96-hour Holter monitoring was used to assess Afib burden.

A little over half (n=1,240; median age 68 years; 34.4% women; 43% with paroxysmal Afib) of the study population qualified for the current analysis by using used the CABANA monitors and providing 90-day post-blanking recordings. Treatment comparisons were performed using a modified ITT approach.

The authors found that both randomized group experienced reduction in Afib burden, the treatment difference was greater in ablation patients, and was significant across the 5 years of follow-up (P<0.01). Additionally, Afib burden was significantly reduced by catheter ablation regardless of the patients’ baseline Afib pattern (paroxysmal or persistent/ long-standing persistent).

“Although Afib burden at baseline was greater in the patients with persistent/long-standing persistent Afib, the absolute magnitude of treatment benefit difference was larger for these patients compared with those with paroxysmal Afib,” they wrote.

The authors also noted that over 5 years, the use of antiarrhythmic drugs tapered to 33% of the drug-therapy group, and the decreasing use of these drugs over time in these patients appeared to have been largely affected by patient crossovers to ablation therapy.

Finally, they stated that “An interesting finding from our study was the small contribution of AFL [atrial flutter] or AT [atrial tachycardia] as the first recurrent atrial arrhythmia type, regardless of randomization. These highly symptomatic rhythms often require repeat ablation and are often seen in patients with persistent or long-standing persistent Afib; these patients are particularly challenging for Afib management.”

Poole and co-authors noted that their results add to the fairly sparse data on Afib burden that come from trials such as MANTRA-PAF, CASTLE-AF, and CIRCA-DOSE.

Study limitations included the fact that 14% of the enrolling sites were unable to use the proprietary CABANA recoding system because of “country-level regulatory restrictions,” so these sites used their standard recording technologies. Also, the authors agreed with Marchlinski’s group that “time to first recurrence of Afib has important limitations as a measure of treatment durability in Afib due to the highly variable nature of the disease.”

Poole and co-authors stated that “More work is needed to understand the relationship between burden of Afib and adverse clinical outcomes from Afib,” such as the temporal relationship of subclinical Afib burden to thromboembolic events with implantable pacemakers or implantable cardioverter defibrillator logs.

  1. Catheter ablation was effective in reducing recurrence of any atrial fibrillation (Afib) by 48% and symptomatic Afib by 51% versus drug therapy over five years of follow-up.

  2. The benefit appeared to be stable over the long-term follow-up period and was not influenced by the uncommon use of antiarrhythmic drugs in the patients undergoing ablation.

Shalmali Pal, Contributing Writer, BreakingMED™

The study was supported by the NIH, St. Jude Medical Drug Foundation, St. Jude Medical, Biosense Webster, Medtronic, and Boston Scientific.

Poole reported support from, and/or relationships with ATriCure, Biotronik, Medtronic, Kestra, Boston Scientific, MediaSphere Medical, and EBR Systems. Co-authors reported support from, and/or relationships with, the NIH, the National Heart, Lung, and Blood Institute, Mayo Clinic, St. Jude Medical, Abbott Medical, Medtronic, Biosense Webster, Johnson & Johnson, Boston Scientific, Cardiofocus, Ventrix, St. Jude Foundation, Thermedical, Merck, Oxygen Therapeutics, Bristol-Myers Squibb, AstraZeneca, the University of Calgary, Eli Lilly, AGA Medical, Tufts University, CeleCore, Amgen, CardioFocus, CardioInsight, Siemens, Endosense, Robertson Foundation, Hansen Medical, Spectrum Dynamics, SigNum Preemptive Healthcare, MediaSphere Medical, Wiley & Sons, Oxford, and External Beam Ablation Medical Devices. One co-author reported patents pending for a catheter for intracardiac imaging and intracardiac electrogram signal analysis.

Marchlinski reported relationships with Medtronic, Abbott, and Biosense Webster. Co-authors reported no relationships relevant to the contents of this paper to disclose.

Cat ID: 913

Topic ID: 74,913,730,913,914,192,925