Cryoablation for paroxysmal atrial fibrillation (PAF) is not the standard of care, but a recent study may change at least some clinicians’ thinking on that score. The STOP-AF First study, which was presented at ESC 2020, demonstrated that cryoablation with the Medtronic Arctic Front device beat medical management decisively for control of atrial fibrillation (AF) in patients with symptomatic PAF who have not undergone drug therapy. However, the rate of adverse events for those on device therapy is less than 2%, making this a safe and effective method for an affliction that plagues millions across the globe.

The STOP-AF First study, sponsored by Medtronic plc, of Dublin, sought to evaluate whether cryoablation performed more effectively than anti-arrhythmic drugs in patients who have not been regularly treated with medical therapy. Oussama Wazni of the Cleveland Clinic said in a presentation at the European Society of Cardiology scientific sessions that data validation for the study was handled by the Cleveland Clinic, adding that the hypothesis behind STOP-AF First is no novelty.

Guidelines still iffy on ablation as first-line therapy

“We as well as others have shown that earlier intervention with catheter ablation may improve long-term efficacy and disease progression,” Wazni said, although he acknowledged that few randomized, controlled trials have been undertaken to evaluate ablation as a first-line treatment for symptomatic, paroxysmal AF. The data for cryoablation are even more lean than the data for RF ablation in this context, however, and thus ablation is a class I recommendation only for drug-refractory patients. The level of evidence for ablation as a first course of therapy enjoys only a B rating, earning this approach to AF only a class IIa endorsement from the European Society of Cardiology.

Wazni said existing data for radio-frequency (RF) ablation suggested a modest benefit in drug treatment-naïve patients, adding that STOP-AF First was designed as a superiority trial matching the device therapy against drug therapy for sustained freedom from AF, atrial tachycardia and atrial flutter. The primary safety objective was to demonstrate “an acceptable safety profile” for the more than 200 patients at 24 sites across the U.S. Patients need not have had no exposure to drug therapy, but cannot have been on an anti-arrhythmic drug for more than seven days prior to randomization. The age range for enrollment was 18-80 years.

Patients were randomized evenly between the two arms, and were checked via 12-lead electrocardiogram (ECG) at baseline and at one-month post-treatment. The patients were followed out to a year with another three ECG check-ups (three, six and 12 months), while continuous ambulatory ECG was invoked at six months for the duration of the one-year follow-up.

Treatment failure was defined as any subsequent AF surgery or ablation in the first 90 days, while treatment failures after 90 days included any documented AF, atrial flutter or atrial tachycardia. Cardioversion and the use of class I or III antiarrhythmic drug (AAD) use after 90 days were also deemed treatment failures for those in the device arm. For safety measures, the pre-specified performance goal was set at less than 12%, with seven-day events including transient ischemic attack, stroke, major bleeding, myocardial infarct and vascular complication. At 12 months, symptomatic pulmonary vein stenosis would be deemed a safety event, as would be atrial-esophageal fistula and unresolved injury to the phrenic nerve.

The final analysis consisted of 203 treated patients, although three in the drug arm and four in the device arm dropped out prior to treatment. Roughly two-thirds of the 99 patients who remained in the medical management arm received flecainide while 13% were administered dronedarone. Wazno remarked that only one patient in this arm received amiodarone, for many years a mainstay for AF patients. Another eight patients in the control arm exited prior to completion of therapy.

Wazni said the primary efficacy endpoint was met with a 75% success rate for cryoablation while AAD achieved only a 45% success rate, although the curves did not appear to begin separating until roughly three months post-randomization. A primary efficacy failure occurred in 26 patients on device therapy, 21 of which were related to arrhythmias, which accounted for 35 of the 51 primary efficacy failures in the drug arm. The complication rate in the device arm was 1.9% (two events), a significant improvement over the performance goal of 12%, for a p score of 0.0001.

Similar skill set between RF, cryoablation

Rob Kowal, chief medical officer of the cardiac electrophysiology divisions at Medtronic, told BioWorld that there is “a uniform basic knowledge set required among electrophysiologists performing catheter ablations,” regardless of the ablation energy. However, Kowal said several studies have demonstrated a greater uniformity of outcomes with cryoablation “across a broader range of operator experience.”

Kowal noted that studies of ablation in patients who either cannot tolerate drug therapy or whose condition does not sustain the benefit of drug therapy typically show superior outcomes for ablation, particularly cryoablation. However, there is also evidence accumulating that backs the notion of ablation progressively earlier in the disease life cycle, hopefully prior to the point at which drug therapy falters. Kowal said that a shorter diagnosis-to-ablation time “is associated with lower rates of arrhythmia recurrence, repeat procedures and hospitalizations.”

The volume of enrollment suggests an average of slightly fewer than 10 patients per site, and Kowal noted that the enrollee range per site ran from a single patient to 38. Kowal said the company has not evaluated whether there is an association between outcomes and volumes, but added that this was not part of the statistical analysis plan.

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