Judy W M Cheng1. 1. Massachusetts College of Pharmacy and Health Sciences, Brigham and Women's Hospital, Boston, MA 02115, USA. judy.cheng@mcphs.edu
Abstract
OBJECTIVE: To review the pharmacology and clinical evidence of the use of vernakalant in the management of atrial fibrillation (AF). DATA SOURCES: Peer-reviewed articles published in the English language were identified from MEDLINE and Current Contents databases (both 1966-March 5, 2008) using the search terms RSD 1235 and vernakalant. Citations from available articles and recent meeting abstracts were reviewed for additional references. During the preparation of this article, vernakalant was being reviewed by the Food and Drug Administration (FDA). Therefore, information posted on the FDA Web site was also evaluated. STUDY SELECTION AND DATA EXTRACTION: Phase 2 and Phase 3 clinical studies of both intravenous and oral vernakalant were reviewed. The design and results of the studies were critically evaluated. DATA SYNTHESIS: Vernakalant is a sodium and ultra-rapid potassium channel blocker with atrial selective effects. In 2 clinical studies evaluating use of intravenous vernakalant in cardioversion of patients with recent-onset AF, vernakalant improved the chance of restoration of normal sinus rhythm (combined results 51% vs 3.8% with placebo; p < 0.001). In postoperative AF, intravenous vernakalant also improved the chance of restoration of normal sinus rhythm (45% vs 15% with placebo; p = 0.0002). Early Phase 2 studies demonstrated that oral vernakalant 300 mg or 600 mg twice daily successfully maintained sinus rhythm compared with placebo. No proarrhythmias relating to vernakalant have been reported to date. Common adverse effects include dysgeusia, sneezing, and paresthesia. CONCLUSIONS: Vernakalant is a new atrial-selective antiarrhythmic agent. Phase 3 clinical trials of the intravenous formulation and early Phase 2 studies of the oral formulation demonstrated vernakalant to be efficacious and safe in converting recent-onset AF to sinus rhythm. Further studies are needed to explore the efficacy and safety of vernakalant use in patients with severe heart failure and AF, as well as its relative efficacy and safety compared with other antiarrhythmic agents, especially with long-term use.
OBJECTIVE: To review the pharmacology and clinical evidence of the use of vernakalant in the management of atrial fibrillation (AF). DATA SOURCES: Peer-reviewed articles published in the English language were identified from MEDLINE and Current Contents databases (both 1966-March 5, 2008) using the search terms RSD 1235 and vernakalant. Citations from available articles and recent meeting abstracts were reviewed for additional references. During the preparation of this article, vernakalant was being reviewed by the Food and Drug Administration (FDA). Therefore, information posted on the FDA Web site was also evaluated. STUDY SELECTION AND DATA EXTRACTION: Phase 2 and Phase 3 clinical studies of both intravenous and oral vernakalant were reviewed. The design and results of the studies were critically evaluated. DATA SYNTHESIS: Vernakalant is a sodium and ultra-rapid potassium channel blocker with atrial selective effects. In 2 clinical studies evaluating use of intravenous vernakalant in cardioversion of patients with recent-onset AF, vernakalant improved the chance of restoration of normal sinus rhythm (combined results 51% vs 3.8% with placebo; p < 0.001). In postoperative AF, intravenous vernakalant also improved the chance of restoration of normal sinus rhythm (45% vs 15% with placebo; p = 0.0002). Early Phase 2 studies demonstrated that oral vernakalant 300 mg or 600 mg twice daily successfully maintained sinus rhythm compared with placebo. No proarrhythmias relating to vernakalant have been reported to date. Common adverse effects include dysgeusia, sneezing, and paresthesia. CONCLUSIONS:Vernakalant is a new atrial-selective antiarrhythmic agent. Phase 3 clinical trials of the intravenous formulation and early Phase 2 studies of the oral formulation demonstrated vernakalant to be efficacious and safe in converting recent-onset AF to sinus rhythm. Further studies are needed to explore the efficacy and safety of vernakalant use in patients with severe heart failure and AF, as well as its relative efficacy and safety compared with other antiarrhythmic agents, especially with long-term use.