Early Catheter Ablation for AF in the EAST-AFNET 4, EARLY-AF, and STOP AF First Trials

Catheter ablation is an established approach for managing patients with AF, with the current guidelines recommending this as a second-line therapy after failure (or intolerance) of anti-arrhythmic drugs (AADs).1 More recently, clinical trials suggested that early catheter ablation can be superior to AADs. As such, EAST-AFNET 4 (Early Treatment of Atrial Fibrillation for Stroke Prevention Trial)2 examined whether an approach of early rhythm-control therapy that includes AF catheter ablation would be associated with better outcomes compared to standard care. Early initiation of rhythm-control therapy was associated with less-frequent cardiovascular events without affecting the in-hospital stay. Of note, the early rhythm-control strategy was associated with more adverse events related to rhythm-control therapy, but the incidence of the overall safety outcome events was not significantly different between the two groups. But the limitations of the study, such as the inclusion of patients with early AF, exclusion of the most symptomatic patients, and the lack of detailed data on AF recurrence in both the study groups, should not be ignored.

Following EAST-AFNET 4, the EARLY-AF (Early Aggressive Invasive Intervention for Atrial Fibrillation) trial3 took it a step farther and challenged the available guidelines by including a cohort of 303 patients with symptomatic paroxysmal AF over a 12-month period of follow-up. A low power to examine cardiovascular outcomes, the use of a single technology ablation, and the limited follow-up period—preventing the authors from studying longer-term effects of early ablation—were significant limitations associated with the study. However, the authors importantly demonstrated that recurrence of atrial tachyarrhythmia occurred in 42.9% patients who underwent ablation as opposed to 67.8% of patients assigned to receive AADs (p < 0.001). Symptomatic atrial tachyarrhythmia had recurred in 11.0% of the patients who underwent ablation and in 26.2% of those who received AADs. Serious complications and side effects occurred in 3.2% of patients who underwent ablation and in 4.0% of patients who received AADs.

To add to the EARLY-AF trial results, in the multi-centre STOP-AF First (Cryoballoon Catheter Ablation in Antiarrhythmic Drug Naive Paroxysmal Atrial Fibrillation) trial,4 the authors aimed to assess the safety and efficacy of catheter ablation compared to ADDs in patients with symptomatic paroxysmal AF. The percentages of patients with treatment success at 12 months were 74.6% in the ablation group and 45% in the AADs group (p < 0.001), suggesting that cryoballoon catheter ablation as initial therapy is superior to AADs for the prevention of atrial arrhythmia recurrence in patients with paroxysmal AF. Importantly, serious procedure-related adverse events were uncommon.

Although the EARLY-AF and STOP-AF First trials were looking at different outcomes and used different monitoring for atrial arrhythmia, both trials suggested that cryoballoon catheter ablation is a more effective first-line approach than AADs by reducing the rate of recurrence by approximately 50%. Without ignoring that an invasive procedure is associated with more upfront risk than medical therapy, the available studies either using cryoballoon or radiofrequency technology (see the recently published study by Kuck et al.5), provide initial data in support of the use of ablation for early management of AF to delay the progression of paroxysmal to persistent AF that is more difficult to treat.

What remains to evaluate is whether the results are generalizable to larger cohorts, older patients, patients with persistent AF, and other ablation technologies, which is critical for a high and reproducible procedural success rate with acceptable safety. Of note, the advantage of the cryoballoon technology is that it is not as dependent on the operator as other types of ablation and may therefore be easier to widely use with good results. Whether we are talking about first-line cryoballoon catheter ablation or first-line radiofrequency catheter ablation, additional large, randomised trials will be needed to compare different ablation technologies with ADDs.

In the future, it may be the case that ablation can be offered to patients with AF without the need to wait for failure of the ADDs approach. Recent studies have been promising and should certainly be taken into consideration when the next guidelines are written, but these studies may not necessarily change the guidelines. The purpose of the guidelines is to enhance appropriateness of practice, improve quality of cardiovascular care, and to lead to better outcomes. However, the guidelines should not limit the cardiologist, who needs to remain flexible when new treatment strategies become available, develop individualised patient approaches, and be open to approaches beyond those suggested by the guidelines.


  1. Hindricks G, Potpara T, Dagres N, et al. ESC Scientific Document Group. 2020 ESC Guidelines for the diagnosis and management of atrial fibrillation developed in collaboration with the European Association for Cardio-Thoracic Surgery (EACTS): The Task Force for the diagnosis and management of atrial fibrillation of the European Society of Cardiology (ESC) Developed with the special contribution of the European Heart Rhythm Association (EHRA) of the ESC. Eur Heart J 2021;42:373-498.
  2. Kirchhof P, Camm AJ, Goette A, et al. EAST-AFNET 4 Trial Investigators. Early Rhythm-Control Therapy in Patients with Atrial Fibrillation. N Engl J Med 2020;383:1305-16.
  3. Andrade JG, Wells GA, Deyell MW, et al. Cryoablation or Drug Therapy for Initial Treatment of Atrial Fibrillation. N Engl J Med 2021;384:305-15.
  4. Wazni OM, Dandamudi G, Sood N, et al. STOP AF First Trial Investigators. Cryoballoon Ablation as Initial Therapy for Atrial Fibrillation. N Engl J Med 2021;384:316-24.
  5. Kuck KH, Lebedev DS, Mikhaylov EN, et al. Catheter ablation or medical therapy to delay progression of atrial fibrillation: the randomized controlled atrial fibrillation progression trial (ATTEST). Europace 2021;23:362-9.

Clinical Topics: Arrhythmias and Clinical EP, Cardiovascular Care Team, EP Basic Science, SCD/Ventricular Arrhythmias, Atrial Fibrillation/Supraventricular Arrhythmias

Keywords: Anti-Arrhythmia Agents, Atrial Fibrillation, Length of Stay, Follow-Up Studies, Catheter Ablation, Heart Atria, Recurrence, Tachycardia, Pharmaceutical Preparations, Reference Standards, Stroke, Longitudinal Studies

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