This meta-analysis assessed the efficacy and safety of vernakalant on conversion of AF to SR. Vernakalant is associated with a stastically significant success in conversion of AF to SR. In this meta-analysis, vernakalant was superior to placebo and amiodarone in converting AF to SR, but there was no difference in adverse effects of cardiac origin between the two groups.
There was one trial [13
] with low quality had included into our analysis, obtaining 1 point in the Jadad scale. This study was not excluded because that paper was a post hoc analysis of ACT I and ACT IV in which ACT I was double-blind while the later was open-label. The remaining 4 trials had Jadad scale of 3 [7
] and 4 [8
] respectively. The meta-analysis of vernakalant efficacy as compared with placebo or amiodarone revealed no heterogeneity (I2
=0%) while there was significant heterogeneity in comparison of AEs of cardiac origin between the two groups (I2
=71%). This may be mainly due to low incidence of AEs of cardiac origin in one trial [11
] and the differences of follow-up time ranging from 1 week to 30 days.
The result of this meta-analysis is in accordance with previous reviews [14
] showing vernakalant is superior to placebo and amiodarone. It is needed to state that the conversion rates with vernakalant were lower in the AVRO [11
] trial than those in a post hoc analysis [13
] of data from ACT I and ACT IV in 3–48 hours’ duration AF patients (51.7% vs 59%) which may be caused by the different medical history, having a higher propotion of patients with CHF included in the AVRO trial (20%) than later study (5%) [11
]. Vernakalant is also superior in achieving SR in patients with post-operative AF enrolled in ACT II as compared with placebo (47% vs 14%) [16
]. The highest efficacy of vernakalant cardioversion rate was observed for AF up to 72 hours (70–80%) [14
] while it was relatively ineffective in AF patients with duration more than 7 days and in atrial flutter, having conversion rates of 8% and 2.5% respectively in ACT I and 9 and 7% respectively in ACT III. Promising results were also obtained by evaluating an oral formulation of vernakalant for the maintenance of SR in phase II, placeo-controlled, dose-ranging studies (300 mg or 600 mg twice daily) [17
]. Vernakalant could achieve rapid termination of AF with median conversion time ranging from 8 min to 12 min while the median conversion time in control groups was much longer over 30 min to over 100 min.
This meta-analysis showed no significant difference in occurring of AEs of cardiac origin between the two arms. The AEs other than cardiac origin was not extracted and analysed due to the presence of patients reporting more than one adverse event. According the trials, the most common drug-related adverse events occurring within the first 24 hours were dysgeusia, sneezing, paraesthesia and cough. Common cardiac disorders resulted in vernakalant groups included bradycardia and atrial flutter. The previous one responded well to discontinuation of vernakalant and/or intravenous atropine while the later was converted to SR with continuation of the infusion of vernakalant. Vernakalant is generally well tolerated in conversion of AF to SR with no significant QTc prolongation and proarrhythmia with the use of this drug have not been reported to date.
Limitations of this study
This study has some limitations. As our paper aimed to include only English full-text articles published in peer-reviewed journals, there is a potential for publication bias. The number of included studies was too low to perform publication bias assessment using funnel plot or other widely accepted statistical methods. However, we can expect that studies excluded from the analysis were small and of low quality. As low-quality studies comprised less than 2% of the whole patient population included into the meta-analysis, the potential effect of lacking studies should be very low. Our study showed that vernakalant is superior to control group and since there was only one study comparing with amiodarone was included in this meta-analysis, further research comparing vernakalant and other antiarrhythmic agents through direct head-to-head comparisons may be needed to confirm this effect. There was no difference shown in safety outcome in this study between the vernakalant and control groups, however, more randomized controlled trials with a longer follow-up are needed to better evaluate the efficacy and safety of vernakalant on atrial fibrillation patients.