Efficacy and Safety of Vernakalant for Cardioversion of Recent-onset Atrial Fibrillation in the Asia-Pacific Region: A Phase 3 Randomized Controlled Trial

Abstract

Atrial fibrillation (AF) is a common clinically significant cardiac arrhythmia. This phase 3 randomized, double-blind, placebo-controlled trial assessed the efficacy and safety of vernakalant hydrochloride for the pharmacological conversion of AF to sinus rhythm in patients with recent-onset (>3 hours to ≤7 days) symptomatic AF from the Asia-Pacific region. Patients received an infusion of vernakalant (3 mg/kg) or placebo for 10 minutes. If AF had not been terminated 15 minutes later, a second infusion of vernakalant (2 mg/kg) or placebo for 15 minutes was administered. The primary efficacy end point was conversion of AF to sinus rhythm for >1 minute within 90 minutes. The study was terminated early for administrative reasons; 123 patients from Korea, Taiwan, and India were randomized to receive vernakalant (n = 55) or placebo (n = 56). A greater proportion of patients who received vernakalant (52.7%) than placebo (12.5%) met the primary end point (P < 0.001), and cardioversion was faster in the vernakalant group than in the placebo group (P < 0.001). Vernakalant was generally well tolerated; the incidence of treatment-emergent adverse events was similar between the groups. We conclude that vernakalant is efficacious in the rapid cardioversion of recent-onset AF in patients from the Asia-Pacific region.

FIGURE 1.

Study population.

FIGURE 2.

Survival curves for time to conversion from atrial fibrillation to sinus rhythm in the (A) 90 minutes and (B) 24 hours after the start of infusion of placebo (P) or vernakalant (V). Patients who received electrical cardioversion or withdrew were censored at the corresponding time.

FIGURE 3.

Proportion of patients reporting no symptoms of atrial fibrillation (AF) at different time points after administration of vernakalant and placebo. Patient numbers are shown in parentheses.