Safety and efficacy of vernakalant for acute cardioversion of atrial fibrillation: an update

Abstract

Yukiomi Tsuji,1 Dobromir Dobrev1–3 1Institute of Pharmacology, Faculty of Medicine, University Duisburg-Essen, Essen, 2Division of Experimental Cardiology, Medical Faculty Mannheim, Heidelberg University, Mannheim, 3Deutsches Zentrum für Herz-Kreislauf-Forshcung [German Center for Cardiovascular Research], partner site Heidelberg/Mannheim, Mannheim, Germany Abstract: Intravenous vernakalant has recently been approved in Europe as an atrial-selective antiarrhythmic drug for the conversion of recent-onset atrial fibrillation (AF). It inhibits atrial-selective K+ currents (IK,ACh and IKur) and causes rate-dependent atrial-predominant Na+ channel block, with only a small inhibitory effect on the rapid delayed rectifier K+ current (IKr) in the ventricle. Due to its atrial-selective properties, vernakalant prolongs the effective refractory period of the atria with minimal effects on the ventricles, being associated with a low proarrhythmic risk for torsades de pointes arrhythmias. Five pivotal clinical trials consistently demonstrated that vernakalant rapidly terminates AF with stable maintenance of sinus rhythm for up to 24 hours. A head-to-head comparative trial showed that the 90-minute conversion rate of vernakalant was substantially higher than that of amiodarone. Initially, a longer-acting oral formulation of vernakalant was shown to be effective and safe in preventing AF recurrence after cardioversion in a Phase IIb study. However, the clinical studies testing oral vernakalant for maintenance of sinus rhythm after AF cardioversion were prematurely halted for undisclosed reasons. This review article provides an update on the safety and efficacy of intravenous vernakalant for the rapid cardioversion of AF. Keywords: atrial fibrillation, antiarrhythmic drug, atrial-selective K+ currents, Na+ channel block, ventricles