Cargando…

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

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 ca...

Descripción completa

Detalles Bibliográficos
Autores principales: Ezekowitz, Michael D., Ellenbogen, Kenneth A., DiMarco, John P., Kaszala, Karoly, Boddy, Alexander, P., Gregory Geba, Koren, Andrew
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer US 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4346668/
https://www.ncbi.nlm.nih.gov/pubmed/25638303
http://dx.doi.org/10.1007/s10840-014-9966-z
_version_ 1782359724590628864
author Ezekowitz, Michael D.
Ellenbogen, Kenneth A.
DiMarco, John P.
Kaszala, Karoly
Boddy, Alexander
P., Gregory Geba
Koren, Andrew
author_facet Ezekowitz, Michael D.
Ellenbogen, Kenneth A.
DiMarco, John P.
Kaszala, Karoly
Boddy, Alexander
P., Gregory Geba
Koren, Andrew
author_sort Ezekowitz, Michael D.
collection PubMed
description 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.
format Online
Article
Text
id pubmed-4346668
institution National Center for Biotechnology Information
language English
publishDate 2015
publisher Springer US
record_format MEDLINE/PubMed
spelling pubmed-43466682015-03-04 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 Ezekowitz, Michael D. Ellenbogen, Kenneth A. DiMarco, John P. Kaszala, Karoly Boddy, Alexander P., Gregory Geba Koren, Andrew J Interv Card Electrophysiol Article 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. Springer US 2015-02-01 2015 /pmc/articles/PMC4346668/ /pubmed/25638303 http://dx.doi.org/10.1007/s10840-014-9966-z Text en © The Author(s) 2015 https://creativecommons.org/licenses/by/4.0/ 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.
spellingShingle Article
Ezekowitz, Michael D.
Ellenbogen, Kenneth A.
DiMarco, John P.
Kaszala, Karoly
Boddy, Alexander
P., Gregory Geba
Koren, Andrew
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
title 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
title_full 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
title_fullStr 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
title_full_unstemmed 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
title_short 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
title_sort 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
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4346668/
https://www.ncbi.nlm.nih.gov/pubmed/25638303
http://dx.doi.org/10.1007/s10840-014-9966-z
work_keys_str_mv AT ezekowitzmichaeld aplacebocontrolleddoubleblindrandomizedmulticenterstudytoassesstheeffectsofdronedarone400mgtwicedailyfor12weeksonatrialfibrillationburdeninsubjectswithpermanentpacemakers
AT ellenbogenkennetha aplacebocontrolleddoubleblindrandomizedmulticenterstudytoassesstheeffectsofdronedarone400mgtwicedailyfor12weeksonatrialfibrillationburdeninsubjectswithpermanentpacemakers
AT dimarcojohnp aplacebocontrolleddoubleblindrandomizedmulticenterstudytoassesstheeffectsofdronedarone400mgtwicedailyfor12weeksonatrialfibrillationburdeninsubjectswithpermanentpacemakers
AT kaszalakaroly aplacebocontrolleddoubleblindrandomizedmulticenterstudytoassesstheeffectsofdronedarone400mgtwicedailyfor12weeksonatrialfibrillationburdeninsubjectswithpermanentpacemakers
AT boddyalexander aplacebocontrolleddoubleblindrandomizedmulticenterstudytoassesstheeffectsofdronedarone400mgtwicedailyfor12weeksonatrialfibrillationburdeninsubjectswithpermanentpacemakers
AT pgregorygeba aplacebocontrolleddoubleblindrandomizedmulticenterstudytoassesstheeffectsofdronedarone400mgtwicedailyfor12weeksonatrialfibrillationburdeninsubjectswithpermanentpacemakers
AT korenandrew aplacebocontrolleddoubleblindrandomizedmulticenterstudytoassesstheeffectsofdronedarone400mgtwicedailyfor12weeksonatrialfibrillationburdeninsubjectswithpermanentpacemakers
AT ezekowitzmichaeld placebocontrolleddoubleblindrandomizedmulticenterstudytoassesstheeffectsofdronedarone400mgtwicedailyfor12weeksonatrialfibrillationburdeninsubjectswithpermanentpacemakers
AT ellenbogenkennetha placebocontrolleddoubleblindrandomizedmulticenterstudytoassesstheeffectsofdronedarone400mgtwicedailyfor12weeksonatrialfibrillationburdeninsubjectswithpermanentpacemakers
AT dimarcojohnp placebocontrolleddoubleblindrandomizedmulticenterstudytoassesstheeffectsofdronedarone400mgtwicedailyfor12weeksonatrialfibrillationburdeninsubjectswithpermanentpacemakers
AT kaszalakaroly placebocontrolleddoubleblindrandomizedmulticenterstudytoassesstheeffectsofdronedarone400mgtwicedailyfor12weeksonatrialfibrillationburdeninsubjectswithpermanentpacemakers
AT boddyalexander placebocontrolleddoubleblindrandomizedmulticenterstudytoassesstheeffectsofdronedarone400mgtwicedailyfor12weeksonatrialfibrillationburdeninsubjectswithpermanentpacemakers
AT pgregorygeba placebocontrolleddoubleblindrandomizedmulticenterstudytoassesstheeffectsofdronedarone400mgtwicedailyfor12weeksonatrialfibrillationburdeninsubjectswithpermanentpacemakers
AT korenandrew placebocontrolleddoubleblindrandomizedmulticenterstudytoassesstheeffectsofdronedarone400mgtwicedailyfor12weeksonatrialfibrillationburdeninsubjectswithpermanentpacemakers