A randomized controlled trial of pulsed field ablation vs antiarrhythmic therapy as a first-line treatment for persistent atrial fibrillation: The AVANT GUARD trial rationale and design

<h2>ABSTRACT</h2><h3>Background</h3> Recent studies have established catheter ablation as a safe and superior alternative to antiarrhythmic drugs (AADs) as a first-line therapy in patients with paroxysmal atrial fibrillation (AF). There are no randomized controlled trials assessing this strategy in patients with persistent AF. <h3>Objective</h3> The aim of this study is to establish the safety and effectiveness of pulsed field ablation (PFA) as a first-line treatment for persistent AF compared to AAD therapy. <h3>Methods</h3> AVANT GUARD (A Prospective Randomized Multicenter Global Study Comparing Pulsed Field Ablation versus Anti-Arrhythmic Drug Therapy as a First Line Treatment for Persistent Atrial Fibrillation) is a multi-center, global, pivotal IDE study that compares the safety and effectiveness of PFA with the pentaspline PFA catheter to AADs as first-line therapy for patients with persistent AF. All patients will receive an implantable cardiac monitor (ICM). The primary safety endpoint, evaluated in PFA subjects, is a composite of defined acute and chronic device- and procedure-related serious adverse events. <h3>Results</h3> The primary effectiveness endpoint, evaluated in randomized PFA and AAD subjects at 12-months follow-up, is a composite of acute and chronic treatment success including freedom from atrial arrhythmia recurrence ≥ 30s (symptomatic) or ≥ 1 hour (asymptomatic), electrical cardioversion, or (re)ablation. <h3>Conclusion</h3> AVANT GUARD will help fill a critical gap in our understanding of treatment approaches and disease progression for persistent AF patients by providing a direct comparison between ablation using PFA versus AAD treatment as a first-line therapy with continuous monitoring to assess outcomes.