Miki Finnin1. 1. College of Pharmacy, University of Oklahoma, Schusterman Center, Tulsa, OK 74135-2512, USA. Miki-Finnin@ouhsc.edu
Abstract
PURPOSE: The pharmacology, pharmacokinetics, safety, clinical efficacy, and role of intravenous vernakalant hydrochloride for the rapid conversion of atrial fibrillation (AF) to normal sinus rhythm are reviewed. SUMMARY: Vernakalant, currently being evaluated by the Food and Drug Administration (FDA), for the termination of atrial fibrillation, differs in pharmacology from other antiarrhythmics; it achieves action potential interference through blockade of sodium and potassium currents. Vernakalant's actions appear to be directed at relatively atrial-selective potassium currents, which result in lengthening of the atrial action potential and prolongation of the atrial action potential plateau, while not significantly affecting the Q-T interval or the ventricular effective refractory period. As a result, the proarrhythmic effects observed with all other agents approved by FDA for the treatment of AF are eliminated. In clinical trials of vernakalant versus placebo, a statistically significant number of patients converted to normal sinus rhythm after receiving vernakalant. For patients with atrial fibrillation continuing for 3-72 hours, the median time to conversion was between 8 and 14 minutes, with 79% of those who converted remaining in sinus rhythm at 24 hours. CONCLUSION: Intravenous vernakalant, a novel, relatively atrial-selective antiarrhythmic agent, appears to offer an effective and safe approach to the rapid conversion of recent-onset AF to normal sinus rhythm.
PURPOSE: The pharmacology, pharmacokinetics, safety, clinical efficacy, and role of intravenous vernakalant hydrochloride for the rapid conversion of atrial fibrillation (AF) to normal sinus rhythm are reviewed. SUMMARY:Vernakalant, currently being evaluated by the Food and Drug Administration (FDA), for the termination of atrial fibrillation, differs in pharmacology from other antiarrhythmics; it achieves action potential interference through blockade of sodium and potassium currents. Vernakalant's actions appear to be directed at relatively atrial-selective potassium currents, which result in lengthening of the atrial action potential and prolongation of the atrial action potential plateau, while not significantly affecting the Q-T interval or the ventricular effective refractory period. As a result, the proarrhythmic effects observed with all other agents approved by FDA for the treatment of AF are eliminated. In clinical trials of vernakalant versus placebo, a statistically significant number of patients converted to normal sinus rhythm after receiving vernakalant. For patients with atrial fibrillation continuing for 3-72 hours, the median time to conversion was between 8 and 14 minutes, with 79% of those who converted remaining in sinus rhythm at 24 hours. CONCLUSION: Intravenous vernakalant, a novel, relatively atrial-selective antiarrhythmic agent, appears to offer an effective and safe approach to the rapid conversion of recent-onset AF to normal sinus rhythm.
Authors: Denis V Abramochkin; Vladislav S Kuzmin; Leonid V Rosenshtraukh Journal: Naunyn Schmiedebergs Arch Pharmacol Date: 2015-06-24 Impact factor: 3.000