The likelihood of recurrence of atrial arrhythmia in patients with persistent atrial fibrillation (AFib) was lower for those who received pulsed field ablation (PFA) as first-line therapy when compared to those who first tried antiarrhythmic drug (AAD) therapy, according to results from the AVANT-GUARD trial published April 25 in NEJM.

Oussama M. Wazni, MD, et al., randomized 310 patients with persistent AFib 2:1 to receive either PFA or AAD. An additional group of 100 patients were enrolled to undergo PFA for the primary safety endpoint alone. All patients received an insertable cardiac monitor. The primary effectiveness endpoint was short-term success – defined as procedural success in the PFA group and the absence of ablation 90 days after treatment initiation in the AAD group – and long-term success – defined as no recurrence of atrial arrhythmias, repeat ablation, or need for AAD from 90 days to 12 months and freedom from amiodarone use at any time.

The authors found that 128 out of 207 patients in the PFA group (Kaplan-Meier estimate, 56%; 95% CI, 48-63) and 40 out of 103 patients in the AAD group (Kaplan-Meier estimate, 30%; 95% CI, 21-40) saw treatment success. The hazard ratio for composite treatment failure was 0.46 (95% CI, 0.33-0.65; p<0.001).

In the PFA group vs. AAD group, recurrence of a symptomatic atrial tachyarrhythmia lasting for at least 30 seconds was seen in 2% and 3% of patients, respectively. For recurrence of asymptomatic atrial tachyarrhythmia lasting for at least one hour, the rates were 30% and 46%, respectively. "With continuous rhythm monitoring by an insertable device, the trial showed that the burden of detected recurrence of atrial tachyarrhythmia during one year of follow up was lower with initial treatment with PFA ablation than with antiarrhythmic drug therapy," note the authors.

Device- and procedure-related adverse events made up the primary safety endpoint, which was observed in 5.1% of patients in the combined PFA group. At 12-months, 45 patients in the PFA group and 20 patients in the AAD group experienced serious adverse events.

The trial temporarily paused after six neurologic events were observed. Enrollment resumed after independent review by two neurologists. Moving forward, the investigators excluded patients with a CHA₂DS₂-VASc score ≥4 and provided additional screening for left atrial thrombus. "The [stroke] event rate in this trial appears to be similar to that observed in previous trials, and no neurologic events were observed after modification of the procedural workflow," write the authors. "Even so, these results highlight the importance of balancing the risks and benefits of earlier intervention as part of the shared decision-making process."