By Michael H. Crawford, MD, Editor
SYNOPSIS: A three-year follow-up of EARLY-AF, a study of relatively young and healthy patients with recent atrial fibrillation, showed cryoablation remains superior to drug therapy for preventing the development of persistent atrial fibrillation.
SOURCE: Andrade JG, Deyell MW, Macle L, et al. Progression of atrial fibrillation after cryoablation or drug therapy. N Engl J Med 2022; Nov 7. doi: 10.1056/NEJMoa2212540. [Online ahead of print].
The Early Aggressive Invasive Intervention for Atrial Fibrillation (EARLY-AF) trial was a study of patients with symptomatic, untreated AF randomized to cryoballoon catheter ablation compared to antiarrhythmic drug therapy. EARLY-AF showed that at one year, initial ablation exhibited a significantly lower rate of AF recurrence vs. antiarrhythmic drug therapy. Andrade et al conducted a three-year follow-up analysis of patients who underwent a continuous rhythm monitor (loop recorder) implantation to determine the effect of initial treatment on progression to persistent AF.
EARLY-AF was an investigator-initiated, multicenter, open-label, randomized trial with blinded endpoint adjudication conducted at 18 centers in Canada. Researchers enrolled adults with symptomatic paroxysmal AF documented at least once in the prior 24 months and who were not taking an antiarrhythmic drug. All patients received an oral anticoagulant prescription if they were older than age 65 years old or recorded a CHADS2 score of 1 or higher. Crossover to the alternate treatment was allowed if the patient experienced a documented episode of AF of longer than 30 seconds of sufficient severity to warrant a change in therapy. The primary endpoint of the study was the first occurrence of persistent AF, defined as continuous for seven days or longer or lasting 48 hours to seven days but requiring cardioversion over the three-year follow-up period. Several secondary endpoints included serious adverse events and healthcare use.
Between 2017 and 2018, the authors enrolled 303 patients in the trial, and 287 completed the 36-month follow-up (average age = 59 years; about 70% were men). Over the three-year follow-up, 42% of the group randomized to antiarrhythmic therapy crossed over to ablation, and 18% of those randomized to ablation underwent a second ablation. Persistent AF occurred in 1.9% of the ablation group and 7.4 % of the drug therapy group (HR, 0.25; 95% CI, 0.09-0.70). The occurrence of any atrial tachyarrhythmia (AF, flutter, atrial tachycardia) during follow-up was 57% in the ablation group and 77% in the drug therapy group (HR, 0.51; 95% CI, 0.38-0.67), of which 89% were adjudicated to be living with AF. At three years, 5% of the ablation group and 17% of the drug group had been hospitalized (HR, 0.31; 95% CI, 0.14-0.66), and serious adverse events had occurred in 4.5% of the ablation group and 10% of the drug group. The authors concluded cryoballoon catheter ablation was superior to antiarrhythmic drug therapy for preventing persistent AF and other atrial tachycardias over a three-year follow-up.
COMMENTARY
This follow-up of EARLY-AF showed the superiority of ablation over drug therapy persists, and the findings are robust, with a number needed to treat of 18. As the trial acronym suggests, these were patients early in their history of AF. They were relatively young for this diagnosis (mean age of 59 years and a history of AF for a median duration of one year). Median CHA2DS2-VASc was 1, less than 10% were living with ischemic heart disease or heart failure, and less than 4% had a prior stroke. Also, mean left atrial volume was 35 mL/m² and left ventricular ejection fraction was 60%. However, three characteristics stood out: 37% had been diagnosed with hypertension, 36% were obese, and 21% had been diagnosed with sleep apnea. Whether efforts were made to address these comorbidities was not addressed in the paper but certainly would be important. Interestingly, alcohol use (a known risk predictor for AF), was not reported. The rates reported in EARLY-AF at three years in the drug therapy group was 7.4% and considerably less in the ablation group (1.9%). These data speak to the relative early stage of AF in the study population (or perhaps improvements in drug therapy).
There were limitations to the EARLY-AF study. This was an intention-to-treat study, but there were considerable crossovers from the drug therapy group to ablation (42%). Thus, the success of drug therapy probably was overestimated, which would tend to minimize the comparative benefit of ablation. Alternatively, drug therapy may not have been sufficiently aggressive. Also, cryoballoon ablation was the only technique used, so the relative success of the more commonly used radiofrequency ablation techniques is unknown. Finally, no other cardiovascular outcomes were reported, which the authors claimed is because the study was underpowered to explore them. Still, it would have been interesting to see the data.
Adverse effects from cryoballoon ablation were infrequent. Surprisingly, there was no pericarditis or stroke/transient ischemic attack (TIA) with ablation. Only two patients required a pacemaker after. There were three stroke/TIA episodes with drug therapy and four pacemaker placements. The authors emphasized this study does not support a conclusion suggesting ablation is an alternative to oral anticoagulation (OAC); all patients who met criteria for OAC in both groups received them. However, ablation largely eliminates the need for antiarrhythmic drugs, which produce considerable adverse effects. Finally, with the cryoballoon technique, a second ablation procedure was necessary during follow up in 18% of patients. All in all, this is a win for ablation as a first-line therapy for younger, healthier patients with recent onset AF.
A three-year follow-up of EARLY-AF, a study of relatively young and healthy patients with recent atrial fibrillation, showed cryoablation remains superior to drug therapy for preventing the development of persistent atrial fibrillation.
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