Hermida JS, Chen J, Meyer C, et al. - Researchers here describe the rationale as well as the design of the international Cryo-FIRST trial, which will be a multi-national randomized controlled trial, to compare antiarrhythmic drug (AAD) treatment vs cryoballoon pulmonary vein isolation as a first-line therapy in treatment naïve patients with atrial fibrillation (AF). The superiority of cryoablation over AAD therapy was hypothesized. Using a 1:1 design, patients will be randomized to test this hypothesis. Experts defined primary efficacy endpoint failure, using a 90-day blanking period, as (at least) one episode of atrial arrhythmia with a duration > 30 sec (reported by 7-day Holter or 12-lead ECG). They will also assess secondary endpoints, which include quality-of-Life, rehospitalization, arrhythmia recurrence rate, healthcare utilization, and left atrial function, as well as adverse events. Overall 218 patients will be enrolled in up to 16 centers. The findings may assist in patient selection for early AF disease treatment via cryoballoon ablation.