Vernakalant

Vernakalant is an investigational mixed ion channel blocker that can terminate acute atrial fibrillation (AF) in humans at 2 to 5 mg/kg and may be more atrial-selective than available agents. In treatment of antiarrhythmic

Chemical cardioversion of recent-onset atrial fibrillation in the emergency department using vernakalant hydrochloride achieves safe and rapid restoration of sinus rhythm and facilitates same day discharge.[Pubmed:28168639]

Ir J Med Sci. 2017 Nov;186(4):903-908.

BACKGROUND: Vernakalant hydrochloride is a rapid-acting antiarrhythmic drug licensed in the EU since 2010 for the conversion of recent-onset atrial fibrillation with proven efficacy and safety when compared with placebo and amiodarone in randomized clinical trials. AIMS: The aim of our study was to determine the feasibility of same day discharge (following 2 h monitoring) from the emergency department after successful cardioversion using Vernakalant hydrochloride. METHODS: Patients with recent-onset atrial fibrillation treated in the emergency department of a large Dublin academic teaching hospital. Patients received a maximum of two weight based 10 min infusions of Vernakalant. Hypotensive events (>30% initial blood pressure), arrhythmias, conversion rates, and time to conversion were recorded. RESULTS: Sinus rhythm was restored in 35 out of 42 patients (83%) in an average of 8.8 min (median 8 min), average CHA2DS2-VASc of 0.92, HAS-BLED of 0.21 and average symptoms duration of 12 h. There were no hypotensive or arrhythmogenic events. 41 out of 42 patients were discharged after 2 h of monitoring. CONCLUSIONS: Vernakalant hydrochloride has provided a quick, safe, and practical means of achieving rapid restoration of sinus rhythm in our ED population with stable recent-onset AF who would otherwise not have undergone routine electrically cardioversion and same day discharge.

Antiarrhythmic effect of vernakalant in an experimental model of Long-QT-syndrome.[Pubmed:27702859]

Europace. 2017 May 1;19(5):866-873.

Aims: The antiarrhythmic drug Vernakalant exerts antiarrhythmic effects in atrial fibrillation. Recent experimental data suggest interactions with the late sodium current and antiarrhythmic effects in ventricular arrhythmias. We aimed at investigating whether treatment with Vernakalant reduces polymorphic ventricular tachycardia (VT) in an experimental model of Long-QT-syndrome (LQTS). Methods and results: Twenty-nine isolated rabbit hearts were assigned to two groups and treated with erythromycin (300 microM, n = 15) or veratridine (0.5 microM, n = 14) after obtaining baseline data. Thereafter, Vernakalant (10 microM) was additionally infused. Infusion of erythromycin or veratridine significantly increased action potential duration (APD90) and QT interval. Erythromycin and veratridine also significantly augmented spatial dispersion of repolarization (erythromycin: +43 ms; veratridine: +55 ms, P < 0.01, respectively) and temporal dispersion of repolarization. After lowering extracellular [K+] in bradycardic hearts, 11 of 15 erythromycin-treated hearts and 4 of 14 veratridine-treated hearts showed early afterdepolarizations and subsequent polymorphic VT. Additional treatment with Vernakalant resulted in a significant reduction of spatial dispersion of spatial dispersion in both groups (erythromycin: -32 ms; veratridine: -35 ms, P < 0.05 each) and a stabilization of temporal dispersion. After additional treatment with Vernakalant, only 5 of 15 erythromycin-treated hearts (P = 0.07) and 1 of 14 veratridine-treated hearts (P = 0.32) presented polymorphic VT. Conclusion: Vernakalant has antiarrhythmic effects in this experimental model of acquired LQTS. A reduction of spatial dispersion of repolarization and a stabilization of temporal dispersion in hearts showing polymorphic VT represent the major underlying electrophysiological mechanisms.

Vernakalant is superior to ibutilide for achieving sinus rhythm in patients with recent-onset atrial fibrillation: a randomized controlled trial at the emergency department.[Pubmed:28175295]

Europace. 2017 Feb 1;19(2):233-240.

Aims: Ibutilide is a rapid-acting antiarrhythmic drug with worldwide use for conversion of recent-onset atrial fibrillation. Vernakalant, approved in the EU in 2010, is likewise used intravenously, with proven efficacy and safety compared with placebo and amiodarone in randomized clinical trials. The aim of our study was to compare the time to conversion and the conversion rate within 90 min in patients with recent-onset atrial fibrillation treated with Vernakalant or ibutilide. Methods and Results: A randomized controlled trial registered at clinicaltrials.gov (NCT01447862) was performed in 100 patients with recent-onset atrial fibrillation treated at the emergency department of a tertiary care hospital. Patients received up to two short infusions of Vernakalant (n = 49; 3 mg/kg followed by 2 mg/kg if necessary) or ibutilide (n = 51; 1 mg followed by another 1 mg if necessary) according to the manufacturer's instructions. Clinical and laboratory variables, adverse events, conversion rates, and time to conversion were recorded. Time to conversion of AF to sinus rhythm was significantly shorter in the Vernakalant group compared with the ibutilide group (median time: 10 vs. 26 min, P = 0.01), and likewise the conversion success within 90 min was significantly higher in the Vernakalant group (69 vs. 43%, log-rank P = 0.002). No serious adverse events occurred. Conclusion: Vernakalant was superior to ibutilide in converting recent-onset atrial fibrillation to sinus rhythm in the emergency department setting.

Efficacy and Safety of Vernakalant for Cardioversion of Recent-onset Atrial Fibrillation in the Asia-Pacific Region: A Phase 3 Randomized Controlled Trial.[Pubmed:27828791]

J Cardiovasc Pharmacol. 2017 Feb;69(2):86-92.

Atrial fibrillation (AF) is a common clinically significant cardiac arrhythmia. This phase 3 randomized, double-blind, placebo-controlled trial assessed the efficacy and safety of Vernakalant hydrochloride for the pharmacological conversion of AF to sinus rhythm in patients with recent-onset (>3 hours to Vernakalant (3 mg/kg) or placebo for 10 minutes. If AF had not been terminated 15 minutes later, a second infusion of Vernakalant (2 mg/kg) or placebo for 15 minutes was administered. The primary efficacy end point was conversion of AF to sinus rhythm for >1 minute within 90 minutes. The study was terminated early for administrative reasons; 123 patients from Korea, Taiwan, and India were randomized to receive Vernakalant (n = 55) or placebo (n = 56). A greater proportion of patients who received Vernakalant (52.7%) than placebo (12.5%) met the primary end point (P < 0.001), and cardioversion was faster in the Vernakalant group than in the placebo group (P < 0.001). Vernakalant was generally well tolerated; the incidence of treatment-emergent adverse events was similar between the groups. We conclude that Vernakalant is efficacious in the rapid cardioversion of recent-onset AF in patients from the Asia-Pacific region.

Vernakalant(RSD-1235) is an investigational mixed ion channel blocker that can terminate acute atrial fibrillation (AF) in humans at 2 to 5 mg/kg and may be more atrial-selective than available agents; in treatment of antiarrhythmic.

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