Randomized, crossover, controlled comparison of oral loading versus intravenous infusion of propafenone in recent-onset atrial fibrillation

A population of 123 patients with recent-onset (< 72 hours) atrial fibrillation (AF) without heart failure was randomly treated with propafenone (PFN3) intravenously (IV) (2 mg/kg bolus followed by 0.0078 mg/kg/min infusion) or in a single oral dose (os) (600 mg) or with placebo (PLA) (phase 1). If AF persisted 8 hours later, patients on active drugs received the alternative formulation (crossover), and patients receiving PLA remained on PLA (phase 2). A 24-hour Holter monitoring was performed and conversion to sinus rhythm (SR) at 2, 4, and 8 hours of each phase was used as the criterion of efficacy. Conversion to SR occurred within 2 hour in 48% of patients with IV-PFN, 15% with os-PFN, and in 17% with PLA (both P < 0.05 vs IV-PFN). Oral PFN was superior to PLA at 4 hours (71% vs 33%, P = 0.001) and 8 hours (78% vs 48%, P < 0.01), and 2 at 8 hours also superior to IV-PFN (53%, P < 0.03). The mean conversion time within 4 hours was shorter with IV-PFN (25 +/- 15') than with os-PFN (167 +/- 166', P < 0.001) or with PLA (156 +/- 107', P < 0.001). The rates of conversion to SR with IV-PFN after os-PFN failure were comparable to PLA at any observation time, whereas nonresponders to IV-PFN who received os-PFN had significantly higher conversion rates than with placebo at both 4 hours (65% vs 19%) and 8 hours (76% vs 24%; both P < 0.045). Neither serious adverse effects nor episodes of regular tachycardia with 2:2 AV conduction were noted. PFN administered intravenously or in a single oral loading dose was safe and efficacious in converting recent-onset AF to SR. The rates of conversion were different with different routes of administration: IV-PFN was superior to os-PFN over a short observation period, while the overall efficacy of os-PFN wets superior at 8 hours.