Cryoballoon Ablation Safe and Effective as First-Line Therapy for Paroxysmal Atrial Fibrillation

Initially treating symptomatic paroxysmal atrial fibrillation (AF) with cryoballoon ablation to isolate the pulmonary vein is more effective in maintaining freedom from arrhythmias than antiarrhythmic drug therapy and entails a low risk of complications.

So conclude multicenter investigators with the randomized controlled STOP AF First trial (NCT03118518), whose primary results were presented August 29 as a late-breaking clinical trial at the virtual European Society of Cardiology Congress 2020. [Editor’s note: The study was since published in full in the New England Journal of Medicine: nejm.org/doi/full/10.1056/NEJMoa2029554.]

“Improvements in the safety and efficacy of cryoballoon catheter ablation in recent years have increased interest in this therapy for atrial fibrillation,” says the study’s national principal investigator, Oussama Wazni, MD, Section Head of Cardiac Electrophysiology and Pacing at Cleveland Clinic, who presented the findings. “This multicenter trial provides good evidence that it is a reasonable first-line option.”

The need for better AF treatment

Cryoballoon catheter ablation is FDA-approved for treating drug-refractory recurrent, symptomatic paroxysmal and persistent atrial fibrillation. While good evidence exists for the role of catheter ablation as a second-line treatment, few randomized controlled trials have evaluated it — particularly cryoballoon catheter ablation — as first-line therapy. Initial trials of radiofrequency catheter ablation have found that it confers a modest benefit compared with antiarrhythmic drug therapy.

“More effective treatment is an ongoing imperative, since atrial fibrillation becomes harder to control as it progresses and late disease is associated with worse outcomes,” notes Dr. Wazni. “Earlier intervention with catheter ablation may improve long-term efficacy and prevent disease progression.”

Study design and results

The prospective STOP AF First trial was conducted at 24 U.S. sites with 203 patients included in the final analysis, all of whom had been randomized to pulmonary vein isolation with cryoballoon ablation (n = 104) or to antiarrhythmic drug (AAD) therapy (n = 99). All subjects had symptomatic paroxysmal AF and were drug-naïve (i.e., < 7 days on an AAD).

Monitoring was with 12-lead ECG at baseline and at one, three, six and 12 months. Subjects also underwent 24-hour continuous ambulatory ECG monitoring at six and 12 months, along with patient-activated transtelephonic ECG monitoring weekly and when symptomatic, starting at month 3.

Efficacy. The primary efficacy endpoint was treatment success at 12 months. Treatment failure was defined as any of the following:

• Acute procedural failure (treatment arm only)
• Subsequent AF surgery or ablation in the left atrium
• Documented AF, atrial tachycardia or atrial flutter after a 90-day blanking period
• Cardioversion after 90-day blanking period
• Class I or III AAD use after 90-day blanking period (treatment arm only)

Freedom from primary efficacy failure at 12 months was achieved by 75% of patients (95% CI, 65% to 82%) in the cryoballoon ablation group versus 45% of patients (95% CI, 35% to 55%) in the AAD group (P < 0.0001 for the difference).

The following primary efficacy failures occurred in the cryoballoon ablation group (in 26 of 104 patients):

• Documented AF, atrial tachycardia or atrial flutter after 90 days (21 patients)
• Acute procedure failure (3 patients)
• Class I or III AAD therapy required after 90 days (2 patients)

The following primary efficacy failures occurred in the AAD group (in 51 of 99 patients):

• Documented AF, atrial tachycardia or atrial flutter after 90 days (35 patients)
• Ablation required in the left atrium (15 patients)
• Cardioversion required after 90 days (1 patient)

Safety. The primary safety endpoint for cryoballoon ablation was a composite of prespecified procedure- and system-related serious adverse events, with a prespecified performance goal of less than 12% incidence.

Only two patients (1.9%; P < 0.0001 compared with the prespecified performance goal) in the cryoballoon ablation arm had a serious adverse event: one developed a significant pericardial effusion within 30 days, and one had a myocardial infarction within seven days. Additionally, a patient in the AAD arm had a major vascular complication following a cryoballoon ablation.

First-line cryoballoon ablation is a good option

According to Dr. Wazni, this prospective randomized trial provides good evidence to support cryoballoon ablation for pulmonary vein isolation as initial therapy for paroxysmal symptomatic AF.

“Our study found that this catheter intervention is safe and effective for symptomatic paroxysmal atrial fibrillation, without the requirement that patients be drug-refractory,” he concludes. “If approved for first-line use, it could provide an important therapy option in this setting.”

The STOP AF First trial was funded by Medtronic.

Image at top courtesy of Medtronic