Vernakalant (RSD1235): a novel, atrial-selective antifibrillatory agent

This review summarizes the mechanistic properties and the recent experience in the development of a new antiarrhythmic agent, RSD1235 (recently named vernakalant), for the acute conversion of atrial fibrillation to sinus rhythm. Atrial fibrillation is the most common sustained cardiac arrhythmia that is observed in clinical practice and is associated with increased morbidity and mortality, resulting from stroke and exacerbation of heart failure. At present, there is a lack of pharmacologic agents that are able to safely and effectively convert the arrhythmia back to sinus rhythm. Vernakalant has the electrophysiologic properties of a multiple ion channel blocker, developed using a novel approach to target potassium channels that are selectively present in human atria rather than ventricles, and using a rate-dependent blocking strategy for its additional sodium channel block. This paper reviews the mechanism of action of this drug, its performance in preclinical models of efficacy and human disease, and its actions on patients in the completed and published preregistration clinical trials for vernakalant. Overall, vernakalant converted 51.5% of patients who had < 7 days duration of atrial fibrillation and it did this without significantly more cardiovascular adverse events than placebo. Therefore, it must be considered as an important new agent for the treatment of this growing health problem.