Efficacy and safety of vernakalant in patients with atrial flutter: a randomized, double-blind, placebo-controlled trial.

Abstract

AIMS:

Vernakalant is a novel, relatively atrial-selective antiarrhythmic agent for conversion of atrial fibrillation (AF) to sinus rhythm. This study examined the safety and efficacy of vernakalant in converting atrial flutter (AFL) to sinus rhythm.

METHODS AND RESULTS:

This was a phase 2/3, randomized, double-blind, placebo-controlled trial. Adults with AFL received either a 10 min infusion of 3.0 mg/kg vernakalant (n = 39) or placebo (n = 15). If AFL or AF persisted at the end of a 15 min observation period, a second 10 min infusion of 2.0 mg/kg vernakalant or placebo was administered. The primary efficacy outcome was the proportion of patients who had treatment-induced conversion of AFL to sinus rhythm for a minimum duration of 1 min within 90 min after the start of the first infusion. No patient in the placebo group met the primary outcome. Only one patient receiving vernakalant (1 of 39, 3%) converted to sinus rhythm. A reduced mean absolute ventricular response rate occurred within 50 min in patients receiving vernakalant (mean change from baseline -8.2 b.p.m.) vs. patients receiving placebo (-0.2 b.p.m.) (P = 0.037). A post-hoc analysis revealed that vernakalant increased AFL cycle length by an average of 55 ms, whereas the AFL cycle length was unchanged in the placebo group (P < 0.001). There was no occurrence of 1 : 1 atrio-ventricular conduction. Dysgeusia and sneezing were the most common treatment-related adverse events, consistent with previous reports.

CONCLUSION:

Vernakalant did not restore sinus rhythm in patients with AFL. Vernakalant modestly slowed AFL and ventricular response rates, and was well tolerated.

• Authors: A John Camm, Egon Toft, Christian Torp-Pedersen, Pugazhendhi Vijayaraman, Steen Juul-Moller, John Ip, Gregory N Beatch, Garth Dickinson, D George Wyse, Scene 2 Investigators
• Journal: Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology (Europace) Vol. 14 Issue 6 Pg. 804-9 (Jun 2012) ISSN: 1532-2092 [Electronic] England
• PMID: 22291438 (Publication Type: Clinical Trial, Phase II, Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Anisoles
• Anti-Arrhythmia Agents
• Placebos
• Pyrrolidines
• vernakalant

Topics

• Aged
• Aged, 80 and over
• Anisoles (administration & dosage, adverse effects)
• Anti-Arrhythmia Agents (administration & dosage, adverse effects)
• Atrial Flutter (drug therapy)
• Double-Blind Method
• Dysgeusia (chemically induced)
• Female
• Heart Atria (drug effects)
• Heart Conduction System (drug effects)
• Humans
• Male
• Middle Aged
• Placebos
• Pyrrolidines (administration & dosage, adverse effects)
• Sneezing
• Treatment Outcome