1. Introduction
Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia affecting approximately 1-2% of the worldwide population [1]. Without appropriate treatment, AF can significantly impact quality of life with risks of recurrences and/or arrhythmia progression reported to be as high as 90% [2, 3]. Catheter ablation has shown to be an effective treatment with superior efficacy compared to antiarrhythmic drugs (AAD) alone for symptomatic AF [4, 5]. The principle aim of AF ablation is to achieve durable circumferential pulmonary vein isolation (PVI), which electrically separates the pulmonary vein (PV) from the left atrium (LA) at the level of PV ostia/antrum. Although AF ablation is considered relatively safe, the procedure is invasive and carries risks of devastating complications such as esophageal-related injuries, pericardial effusion with tamponade, pulmonary vein stenosis, and cerebrovascular accident [6, 7]. Because of this, ablation is typically utilized in patients who failed initial AAD therapy, and most evidence supporting the use and the superiority of ablation was derived from populations that had already received an AAD as the first-line rhythm-based treatment [8, 9].
Similarly, previously published randomized controlled trials (RCTs) suggest that pulmonary vein isolation is superior to AAD even as initial therapy for paroxysmal atrial fibrillation (pAF). These include the Radiofrequency Ablation vs Antiarrhythmic Drugs as First-Line Treatment of Paroxysmal Atrial Fibrillation (RAAFT-2) trial, the Medical Antiarrhythmic Treatment or Radiofrequency Ablation in Paroxysmal Atrial Fibrillation (MANTRA-PAF) trial, and the Radiofrequency Ablation vs Antiarrhythmic Drugs as First-line Treatment of Symptomatic Atrial Fibrillation (RAAFT-1) trial [10-12]. A meta-analysis of the 3 RCTs by Hakalathi et al. confirmed this finding but reported that ablation was associated with more serious adverse events [13]. However, all 3 RCTs were done using only radiofrequency ablation without any trial performing cryoablation. Moreover, the authors did not perform time-to-event analysis for the main outcome of arrhythmic recurrence. In this updated meta-analysis, we included 2 recently published RCTs that use cryoballoon ablation, the Early Aggressive Invasive Intervention for Atrial Fibrillation (EARLY-AF) trial and the Cryoballoon Catheter Ablation in an Antiarrhythmic Drug Naive Paroxysmal Atrial Fibrillation (STOP AF First) trial and perform a sensitivity-analysis to compare arrhythmia-free survival and to evaluate adverse events between the two strategies [14, 15].