Vernakalant is superior to ibutilide for achieving sinus rhythm in patients with recent-onset atrial fibrillation: a randomized controlled trial at the emergency department

Abstract

Aims: Ibutilide is a rapid-acting antiarrhythmic drug with worldwide use for conversion of recent-onset atrial fibrillation. Vernakalant, approved in the EU in 2010, is likewise used intravenously, with proven efficacy and safety compared with placebo and amiodarone in randomized clinical trials. The aim of our study was to compare the time to conversion and the conversion rate within 90 min in patients with recent-onset atrial fibrillation treated with vernakalant or ibutilide.

Methods and results: A randomized controlled trial registered at clinicaltrials.gov (NCT01447862) was performed in 100 patients with recent-onset atrial fibrillation treated at the emergency department of a tertiary care hospital. Patients received up to two short infusions of vernakalant (n = 49; 3 mg/kg followed by 2 mg/kg if necessary) or ibutilide (n = 51; 1 mg followed by another 1 mg if necessary) according to the manufacturer's instructions. Clinical and laboratory variables, adverse events, conversion rates, and time to conversion were recorded. Time to conversion of AF to sinus rhythm was significantly shorter in the vernakalant group compared with the ibutilide group (median time: 10 vs. 26 min, P = 0.01), and likewise the conversion success within 90 min was significantly higher in the vernakalant group (69 vs. 43%, log-rank P = 0.002). No serious adverse events occurred.

Conclusion: Vernakalant was superior to ibutilide in converting recent-onset atrial fibrillation to sinus rhythm in the emergency department setting.

Figure 1

Timeline of therapeutic intervention. Time schedule and dose of treatment interventions in the two treatment groups.

Figure 2

Patient flow diagram. Screening, enrolment, randomization, and inclusion into further analysis. One patient within the ibutilide group did not receive second study drug due to occurrence of recurrent nsVT.

Figure 3

Conversion to sinus rhythm according to study treatment. Time to treatment-induced conversion from AF to SR within 90 min. x-axis: time from start of first infusion (minutes); y-axis: proportion of patients with conversion to sinus rhythm (95% CI).

Figure 4

Heart rate (A) and blood pressure (B) over 6 h after administration of first study drug infusion. Absolute values and mean change from baseline within 360 min after administration of first study drug infusion.

Figure 5

Mean QT interval (A) and QTcF interval (B) over 6 h after administration of first study drug infusion. Absolute values and mean change from baseline within 360 min after administration of first study drug infusion. (B) Mean QT interval corrected for heart rate using Fridericia's formula.