Results from two studies published in the New England Journal of Medicine support the use of catheter cryoballoon ablation over antiarrhythmic therapy as initial therapy for patients with symptomatic, paroxysmal atrial fibrillation (AFib). The research was based on two trials, known as EARLY-AF and STOP AF First, which both showed that initial use of cryoablation resulted in a significantly lower rate of AFib recurrence compared with drug therapy without increasing the risk for serious adverse events. “We can now offer pulmonary vein isolation–based ablation with greater confidence as first-line therapy for selected patients with paroxysmal atrial fibrillation, particularly those who are disinclined to take antiarrhythmic drugs,” said Joseph E. Marine, MD, from the division of cardiology at Johns Hopkins University School of Medicine, in an accompanying editorial. “The new data will inform shared decision-making discussions with all patients with paroxysmal atrial fibrillation.” The EARLY-AF (Early Aggressive Invasive Intervention for Atrial Fibrillation) trial included 303 adult patients with symptomatic, paroxysmal, untreated AFib who were randomized to catheter ablation with a cryothermy balloon (n = 154) or antiarrhythmic drug therapy (n = 149) as their initial rhythm control. Patients were followed for 12 months. The primary endpoint was the first documented recurrence of any atrial tachyarrhythmia (i.e., AFib, atrial flutter, or atrial tachycardia) lasting 30 seconds or longer between 91 and 365 days after catheter ablation or initiation of an antiarrhythmic drug. At 1 year, documented recurrence occurred in 42.9% of patients who underwent cryoablation compared with 67.8% in the antiarrhythmic group (hazard ratio 0.48 [95% CI 0.35–0.66]). The occurrence of serious adverse events was similar among the two groups: 3.2% of patients in the cryoablation group and 4.0% of patients in the antiarrhythmic group. The STOP AF First (Cryoballoon Catheter Ablation in Antiarrhythmic Drug Naive Paroxysmal Atrial Fibrillation) trial included 203 adult patients with paroxysmal AFib who had not previously received rhythm-control therapy. They were randomized to treatment with a class I or III antiarrhythmic (n = 99) or cryoballoon ablation (n = 104). The results were similar to those of the EARLY-AF trial. A higher percentage of patients in the cryoballoon ablation group had treatment success, defined as freedom from initial failure of the procedure or atrial arrhythmia recurrence after a 90-day period. The estimated percentage of treatment success at 12 months was 74.6% in the ablation group compared with 45.0% in the drug therapy group. Serious adverse events occurred in 14% of patients in both treatment groups. AFib is common, affecting approximately 0.4% to 1% of the general U.S. population, and recurrence rates are high, especially in individuals who are not receiving preventive treatments. Current guidelines by the American Heart Association/American College of Cardiology/Heart Rhythm Society and European Society of Cardiology have generally recommended the use of antiarrhythmic drugs as initial therapy for maintenance of sinus rhythm in patients with AFib. However, these medications tend to have limited efficacy and substantial adverse effects. Once an initial course of treatment fails, catheter ablation is superior to antiarrhythmic drug therapy for preventing further recurrences of atrial arrhythmias. Results of the EARLY-AF and STOP AF First trials could result in some modifications to these current recommendations, with catheter cryoballoon ablation used as initial management to prevent AFib recurrences in select patients. In his editorial, Marine noted that clinicians should consider the populations included in these trials when applying the data in clinical practice. As in the trials, most patients will need to have normal left ventricular function, normal left atrial size, and few coexisting conditions to be eligible for cryoablation. The results cannot be readily extrapolated to patients with persistent AFib, significant structural heart disease, or substantial coexisting conditions that may reduce the efficacy and safety of ablation. Clinicians will need to discuss with patients the benefits and risks of cryoablation compared with initial use of antiarrhythmic therapy. A shared clinical decision-making approach may be beneficial.