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

Abstract

AimsIbutilide 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 resultsA 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.ConclusionVernakalant was superior to ibutilide in converting recent-onset atrial fibrillation to sinus rhythm in the emergency department setting.

Hemodynamic effects of Vernakalant in cardio-surgical ICU-patients treated for recent-onset postoperative atrial fibrillation

“…Favourable efficacy. Times-to-conversion and efficacy data in our patient collective were comparable to previous results from our site 19 , whereas international efficacy data on Vernakalant is more variable, with a majority reporting conversion rates of around 50% 19,22 and only sporadic reports of rates up to 70% and more 19,23 . As reported previously 18 , superior efficacy rates potentially result from a shorter AF-duration prior to conversion (in our population a median of 3.5 h).…”

“…No proarrhythmic effect of Vernakalant could be observed in our study collective, probably due to the relative atrial selectivity of the drug 25,26 . Minor adverse events including sneezing, dysgeusia and nausea, were lying within the known side effect profile of Vernakalant that is caused by inhibition of sodium-channels in the central nervous system 19,27 .…”

“…Typical episodes of hypotension after administrating Vernakalant occur during or immediately after the infusion and are usually transient and fluid-responsive 12,16,28 . Moreover, a general slight decrease in blood pressure lasting several hours after administration of Vernakalant and rare cases of severe events of hypotension and cardiac shock have been published 12,14,19,24 . Whereas short BP-drops during and immediately after cardioversion could be an expression of atrial stunning and therefore reduced cardiac output 29,30 , a long-lasting reduction in BP could be mediated through reduced sympathetic impulses or reduced activation of the RAAS 31 .…”

“…We did not include patients with atrial flutter as Vernakalant is not indicated in this patient group due to lack of efficacy 18 . By revision of arterial blood gas samples prior to inclusion, normal range potassium and magnesium levels were ensured or rebalanced as previously described elsewhere 19 . Vernakalant was administered by the treating physician intravenously as instructed by the manufacturer: up to two infusions (if POAF persisted) of Vernakalant (3 mg/kg the first and the second 2 mg/kg) in 100 ml of normal saline with an interruption of 15 minutes in between.…”

2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS

“…Alternatywny lek to ibutilid, jeżeli jest on dostępny, ale jego stosowanie wiąże się z ryzykiem wystąpienia torsade de pointes [615]. Wernakalant [602][603][604][605] można podawać pacjentom z mało nasiloną niewydolnością serca (I lub II klasa wg NYHA), włącznie z pacjentami z chorobą niedokrwienną serca, pod warunkiem że nie stwierdza się u nich niskich wartości ciśnienia tętniczego ani ciężkiej stenozy aortalnej [616][617][618]. Amiodaron można stosować u pacjentów z niewydolnością serca lub chorobą niedokrwienną serca (choć pacjentów z ciężką niewydolnością serca wykluczano z większości prób klinicznych kardiowersji AF) [596].…”