A placebo-controlled, double-blind, randomized, multicenter study to assess the effects of dronedarone 400 mg twice daily for 12 weeks on atrial fibrillation burden in subjects with permanent pacemakers

Authors

Michael D. Ezekowitz, Thomas Jefferson University
Kenneth Ellenbogen , M.D., Virginia Commonwealth UniversityFollow
John P. DiMarco, University of Virginia - Main Campus
Karoly Kaszala, Hunter Holmes McGuire VA Medical Center
Alexander Boddy, Sanofi-aventis US
Gregory Geba P., Sanofi-aventis US
Andrew Koren, Sanofi-aventis US

Document Type

Article

Original Publication Date

2014

Journal/Book/Conference Title

Journal of Interventional Cardiac Electrophysiology

Volume

42

Comments

Originally published at https://dx.doi.org/10.1007/s10840-014-9966-z

Date of Submission

December 2015

Abstract

Purpose

Dronedarone is a benzofuran derivative with a pharmacological profile similar to amiodarone but has a more rapid onset of action and a much shorter half-life (13–19 h). Our goal was to evaluate the efficacy of dronedarone in atrial fibrillation (AF) patients using dual-chamber pacemakers capable of quantifying atrial fibrillation burden.

Methods

Pacemakers were adjusted to optimize AF detection. Patients with AF burden >1 % were randomized to dronedarone 400 mg twice daily (BID) or placebo. Pacemakers were interrogated after 4 and 12 weeks of treatment. The primary endpoint was the change in AF burden from baseline over the 12-week treatment period. Patients with permanent AF, severe/recently decompensated heart failure, and current use of antiarrhythmic drugs were excluded. AF burden was assessed by a core laboratory blinded to treatment assignment.

Results

From 285 patients screened, 112 were randomized (mean age 76 years, 60 % male, 84 % hypertensive, 65 % with sick sinus syndrome, 26 % with diabetes mellitus type II, 15 % with heart failure). Baseline mean (SEM) AF burden was 8.77 % (0.16) for placebo and 10.14 % (0.17) for dronedarone. Over the 12-week study period, AF burden compared to baseline decreased by 54.4 % (0.22) (P = 0.0009) with dronedarone and trended higher by 12.8 % (0.16) (P = 0.450) with placebo. The absolute change in burden was decreased by 5.5 % in the dronedarone group and increased by 1.1 % in the placebo group. Heart rate during AF was reduced to approximately 4 beats/min with dronedarone (P = 0.285). Adverse events were higher with dronedarone compared to placebo (65 vs 56 %).

Conclusions

Dronedarone reduced pacemaker-assessed the relative AF burden compared to baseline and placebo by over 50 % during the 12-week observation period.

Rights

Copyright © The Author(s) 2015 Open Access This article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited.

Is Part Of

VCU Human and Molecular Genetics Publications