June 2026
Is pulse field ablation better first-line therapy than medication for persistent AF?
By Rebecca Jenkins
Patients with persistent atrial fibrillation (AF) have a significantly lower risk of atrial tachyarrhythmia recurrence if they receive pulsed field ablation (PFA) as a first-line therapy rather than medication, a randomised controlled trial reported in The New England Journal of Medicine finds.
In the international AVANT-GUARD trial (A Prospective Randomized Multicenter Global Study Comparing Pulsed Field Ablation versus Anti-Arrhythmic Drug Therapy as a First-Line Treatment for Persistent Atrial Fibrillation), patients with previously untreated persistent AF were randomly assigned in a 2:1 ratio to receive PFA performed with a pentaspline catheter or to receive antiarrhythmic-drug therapy.
Using continuous rhythm monitoring via an insertable device, the industry-supported trial showed that the burden of detected recurrence of atrial tachyarrhythmia during one year of follow up was lower with initial treatment with PFA.
At 12 months, treatment success was observed in 128 of 207 patients (Kaplan-Meier estimate, 56%) in the PFA group and in 40 of 103 patients (Kaplan-Meier estimate, 30%) in the medication group.
The mean difference in arrhythmia burden was 6.5 percentage points lower after PFA, with more patients in the PFA group having an arrhythmia burden of 0.1% or less.
In the PFA group 35% had an atrial tachyarrhythmia of more than 0.1% compared with 53% of patients in the antiarrhythmic-drug therapy group.
Professor Peter Kistler, Head of Clinical Electrophysiology Research at the Baker Heart and Diabetes Institute, Melbourne, welcomed the study, but said there were some important caveats to the findings, including that the trial was paused midway after six strokes were reported in the PFA group.
‘The periprocedural anticoagulation was tightened and patients with a CHA2DS2-VASc score of 4 or more were excluded,’ he said.
‘Nonetheless the incidence of stroke was 2%, which is much higher than expected in clinical practice as an electrophysiologist commonly performing AF ablation. This compares to 0% in the drug arm.’
Professor Kistler noted that amiodarone, the most effective antiarrhythmic drug, was not permitted as first-line therapy in the group randomised to antiarrhythmic drug therapy.
‘In addition, 98% of patients with recurrent AF in either treatment arm of the study were asymptomatic during monitoring. This is likely explained by minimally or asymptomatic AF patients being recruited into the study. Generally, the main indication for AF ablation is symptoms.’
Many randomised studies had shown that AF ablation was unequivocally the most effective tool in restoring and maintaining sinus rhythm in people with AF, Professor Kistler said.
‘As medication is less effective and may be associated with side effects, there is interest in first-line ablation therapy,’ he told Medicine Today.
‘There is also an argument that intervening early may improve outcomes, but there are limited randomised [trial] data to support this assertion.’
However, given the study’s limitations, Professor Kistler said more evidence was needed before PFA was established as a first-line therapy in this patient population.
He also stressed that the major indication for AF ablation, including PFA, was for patients with symptoms.
‘In persistent AF, the most common symptoms are shortness of breath and fatigue, not palpitations,’ he said. ‘Additionally, any patients with poor left ventricular function gain significant benefits with AF ablation.’
PFA had largely replaced thermal ablation in most hospitals in Australia, Professor Kistler added.
Randomised studies had not shown the technique was more effective than thermal ablation, but it was faster. It also avoided some of the complications of thermal ablation, although the technique had unique complications of its own, he said.