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

Vasc Health Risk Manag. 2013:9:165-75. doi: 10.2147/VHRM.S43720. Epub 2013 Apr 23.

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 (I(K,ACh) and I(Kur)) and causes rate-dependent atrial-predominant Na(+) channel block, with only a small inhibitory effect on the rapid delayed rectifier K(+) current (I(Kr)) 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: Na+ channel block; antiarrhythmic drug; atrial fibrillation; atrial-selective K+ currents; ventricles.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Action Potentials
  • Animals
  • Anisoles / administration & dosage
  • Anisoles / adverse effects
  • Anisoles / therapeutic use*
  • Anti-Arrhythmia Agents / administration & dosage
  • Anti-Arrhythmia Agents / adverse effects
  • Anti-Arrhythmia Agents / therapeutic use*
  • Atrial Fibrillation / diagnosis
  • Atrial Fibrillation / drug therapy*
  • Atrial Fibrillation / physiopathology
  • Heart Conduction System / drug effects*
  • Heart Conduction System / physiopathology
  • Humans
  • Infusions, Intravenous
  • Potassium Channel Blockers / administration & dosage
  • Potassium Channel Blockers / adverse effects
  • Potassium Channel Blockers / therapeutic use*
  • Pyrrolidines / administration & dosage
  • Pyrrolidines / adverse effects
  • Pyrrolidines / therapeutic use*
  • Refractory Period, Electrophysiological
  • Sodium Channel Blockers / administration & dosage
  • Sodium Channel Blockers / adverse effects
  • Sodium Channel Blockers / therapeutic use*
  • Time Factors
  • Treatment Outcome

Substances

  • Anisoles
  • Anti-Arrhythmia Agents
  • Potassium Channel Blockers
  • Pyrrolidines
  • Sodium Channel Blockers
  • vernakalant