Vernakalant: Conversion of atrial fibrillation in patients with ischemic heart disease
Introduction
Cardioversion of AF is a frequent procedure performed in cardiology and emergency departments. Early conversion of AF to sinus rhythm (SR) improves symptoms, prevents the detrimental effects of prolonged AF, and avoids hospitalization [1], [2]. Although electrical cardioversion is highly effective, it requires sedation or anesthesia [3]. Currently available antiarrhythmic agents for pharmacological cardioversion of AF are only moderately effective and may be limited in use by delayed onset of action, as well as proarrhythmic risk which becomes more evident when used in patients with underlying heart disease [3], [4], [5]. There is a need for a safe and effective antiarrhythmic agent for the acute conversion of AF that can be used in a broad patient population, including those with IHD.
Vernakalant is a novel antiarrhythmic agent that acts by blocking early-activating potassium channels combined with concentration-, voltage-, and frequency-dependent blockade of sodium channels [6]. Vernakalant demonstrates preferential effects for atrial tissue (particularly during AF) and has limited actions on ventricular tissue, as it has been shown to selectively prolong the atrial refractory period and rate-dependently slow atrial conduction without affecting ventricular refractoriness [6], [7], [8]. Although vernakalant causes minor blockade of the rapidly activating delayed rectifier current IKr, the late sodium channel block associated with vernakalant offsets the inhibition of IKr, reducing the risk of QT prolongation [6]. Intravenous vernakalant was well tolerated in placebo-controlled clinical trials [9], [10], [11], [12] and rapidly and effectively converted recent onset AF (> 3 h to ≤ 7 days duration); however, there was lower efficacy in longer duration AF and a lack of efficacy in atrial flutter (AFL).
There are limited data available on the efficacy and safety of antiarrhythmic agents in patients who have IHD. This analysis was conducted to assess the efficacy and safety of intravenous vernakalant for the rapid conversion of AF to SR in patients with a history of IHD.
Section snippets
Patient population
Data from the Atrial arrhythmia Conversion Trial I (ACT I) [10], ACT II [9], ACT III [12], ACT IV [13], and Scene 2 (unpublished) clinical studies were combined. These were multicenter, randomized, double-blind, placebo-controlled, parallel group studies, with the exception of ACT IV, which was an open label, single arm study. These studies were designed to assess the efficacy and safety of vernakalant injection in patients with AF or AFL of > 3 h to ≤ 45 days duration (ACT I, ACT III, ACT IV, and
Study Population
The 5 clinical studies included in this analysis were conducted from August 2003 to February 2007. The efficacy population consisted of 707 patients, of which 188 patients (64 placebo, 124 vernakalant) had a history of IHD and 519 patients (145 placebo, 374 vernakalant) did not have IHD (Table 1). The pooled safety population consisted of 1052 patients, of which 274 patients (91 placebo, 183 vernakalant) had a history of IHD and 778 patients (224 placebo, 554 vernakalant) did not have IHD (
Efficacy and safety
In this post-hoc analysis, the safety and efficacy of vernakalant injection were not influenced by a history of IHD. Conversion rates were higher in AF patients who received vernakalant compared to placebo, both in those patients with and those without IHD; the treatment difference did not significantly differ between the IHD group and the non-IHD group. In the ACT II study alone, however, higher efficacy was observed in the IHD group compared to the non-IHD group (which was essentially
Conclusions
This analysis demonstrates that vernakalant injection is effective for the acute conversion of AF to SR, and is safe and well tolerated, in AF/AFL patients with IHD. Vernakalant provides an effective therapeutic alternative for the conversion of AF, with an acceptable safety profile in patients with a history of IHD.
Acknowledgments
The authors of this manuscript have certified that they comply with the Principles of Ethical Publishing in the International Journal of Cardiology, and thank Anjie Moore for assistance in preparing the manuscript.
References (20)
- et al.
Acute treatment of atrial fibrillation
Am J Cardiol
(1998) - et al.
ACC/AHA/ESC 2006 guidelines for the management of patients with atrial fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Revise the 2001 Guidelines for the Management of Patients With Atrial Fibrillation)
J Am Coll Cardiol
(2006) Impact of structural heart disease on the selection of class III antiarrhythmics for the prevention of atrial fibrillation and flutter
Am Heart J
(1998)- et al.
A randomized, controlled trial of RSD1235, a novel anti-arrhythmic agent, in the treatment of recent onset atrial fibrillation
J Am Coll Cardiol
(2004) - et al.
Usefulness of vernakalant hydrochloride injection for rapid conversion of atrial fibrillation
Am J Cardiol
(2010) - et al.
A multicenter, open-label study of vernakalant for the conversion of atrial fibrillation to sinus rhythm
Am Heart J
(2010) Safety considerations in the pharmacological management of atrial fibrillation
Int J Cardiol
(2008)- et al.
Atrial fibrillation in congestive heart failure: current management
Cardiol Clin
(2009) - et al.
Amiodarone as a first-choice drug for restoring sinus rhythm in patients with atrial fibrillation: a randomized, controlled study
Chest
(2000) - et al.
Emergency management of atrial fibrillation
Postgrad Med J
(2003)