A randomized active-controlled study comparing the efficacy and safety of vernakalant to amiodarone in recent-onset atrial fibrillation

Abstract

Objectives: This randomized double-blind study compared the efficacy and safety of intravenous vernakalant and amiodarone for the acute conversion of recent-onset atrial fibrillation (AF).

Background: Intravenous vernakalant has effectively converted recent-onset AF and was well tolerated in placebo-controlled studies.

Methods: A total of 254 adult patients with AF (3 to 48 h duration) eligible for cardioversion were enrolled in the study. Patients received either a 10-min infusion of vernakalant (3 mg/kg) followed by a 15-min observation period and a second 10-min infusion (2 mg/kg) if still in AF, plus a sham amiodarone infusion, or a 60-min infusion of amiodarone (5 mg/kg) followed by a maintenance infusion (50 mg) over an additional 60 min, plus a sham vernakalant infusion.

Results: Conversion from AF to sinus rhythm within the first 90 min (primary end point) was achieved in 60 of 116 (51.7%) vernakalant patients compared with 6 of 116 (5.2%) amiodarone patients (p < 0.0001). Vernakalant resulted in rapid conversion (median time of 11 min in responders) and was associated with a higher rate of symptom relief compared with amiodarone (53.4% of vernakalant patients reported no AF symptoms at 90 min compared with 32.8% of amiodarone patients; p = 0.0012). Serious adverse events or events leading to discontinuation of study drug were uncommon. There were no cases of torsades de pointes, ventricular fibrillation, or polymorphic or sustained ventricular tachycardia.

Conclusions: Vernakalant demonstrated efficacy superior to amiodarone for acute conversion of recent-onset AF. Both vernakalant and amiodarone were safe and well tolerated in this study. (A Phase III Superiority Study of Vernakalant vs Amiodarone in Subjects With Recent Onset Atrial Fibrillation [AVRO]; NCT00668759).