Rates of atrial tachyarrhythmia recurrence were found to be lower in patients receiving catheter cryoballoon ablation vs antiarrhythmic pharmacotherapy as first-line intervention for treatment-naive, symptomatic, paroxysmal atrial fibrillation (AF), according to a study published in The New England Journal of Medicine.

Current guidelines for AF recommend clinicians initiate at least 1 antiarrhythmic drug prior to considering catheter ablation. Investigators sought to determine the effectiveness of cryoablation vs antiarrhythmics for sinus rhythm maintenance during initial treatment of AF.

In the multicenter, open-label, randomized Early Aggressive Invasive Intervention for Atrial Fibrillation trial (EARLY-AF; ClinicalTrials.gov Identifier: NCT02825979), conducted between January 2017 and December 2018, 303 adults with untreated, symptomatic, paroxysmal AF were enrolled and randomly assigned 1:1 to receive initial treatment with cryothermy balloon catheter ablation (n=154; mean age, 57.7±12.3 years; 72.7% men) or antiarrhythmic drug therapy (n=149; mean age, 59.5±10.6 years; 68.5% men). The choice of medication in the latter group was according to local practice (flecainide at 200 mg daily median dose was most common), with a 3-month up-titration toward the maximally tolerated dose. A continuous cardiac monitoring device was implanted in all participants for the detection of atrial tachyarrhythmia.

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Patients were followed for 12 months. The primary study outcome was the first recurrence, between 91 and 365 days after ablation or drug initiation (following a 90-day blanking period), of any form of atrial tachyarrhythmia (AF, atrial tachycardia or atrial flutter) lasting ≥30 seconds. Secondary outcomes included AF burden (% of time spent in AF), quality of life measures, and freedom from symptomatic AF.

After 1 year, atrial tachyarrhythmia recurrence was reported in 42.9% and 67.8% of patients receiving ablation and pharmacotherapy, respectively (24.9% between-group difference; hazard ratio [HR], 0.48; 95% CI, 0.35-0.66; P <.001).

Recurrence of symptomatic atrial tachyarrhythmia at 1 year occurred in 11.0% and 26.2% of patients receiving ablation and pharmacotherapy, respectively (HR, 0.39; 95% CI, 0.22-0.68). Participants in the ablation group spent a median of 0% of time in AF (interquartile range, 0-0.08), and those in the medication group were in AF for a median of 0.13% of the time (interquartile range, 0-1.60; between-group absolute difference treatment effect [β coefficient], -3.3±1.0).

Serious adverse events related to study interventions were reported in 3.2% and 4.0% of patients in the ablation and medication groups, respectively (relative risk, 0.81; 95% CI, 0.25-2.59). No thromboembolic complications or procedural fatalities occurred in either group.

Study limitations include a lack of power to explore cardiovascular outcomes, potential non-generalizability to other ablation technologies, short follow-up period that precluded examination of longer-term effects, and inability to evaluate AF burden change from baseline.

“In this randomized trial involving patients with untreated paroxysmal atrial fibrillation, catheter cryoballoon ablation resulted in a significantly lower rate of recurrence of atrial tachyarrhythmia, as assessed by continuous cardiac rhythm monitoring, than antiarrhythmic drug therapy,” noted the authors.

Funding and Conflicts of Interest Disclosures:

The trial was funded by a peer-reviewed grant from the Cardiac Arrhythmia Network of Canada, unrestricted grants from Medtronic and Baylis Medical, and in-kind support from Medtronic and the University of British Columbia.

Please see original article for conflict of interest declarations.


Andrade JG, Wells GA, Deyell MW, et al. Cryoablation or drug therapy for initial treatment of atrial fibrillation. N Engl J Med. 2021;384(4):305-315. doi:10.1056/nejmoa2029980