Acute dronedarone is inferior to amiodarone in terminating and preventing atrial fibrillation in canine atria.
BACKGROUND
Dronedarone is approved by the U.S. Food and Drug Administration for the treatment of patients with atrial fibrillation (AF) as a safe alternative to amiodarone. There are no full-length published reports describing the effectiveness of acute dronedarone use against AF in experimental or clinical studies.


OBJECTIVE
The purpose of this study was to determine the effect of acute dronedarone and amiodarone on electrophysiological parameters, and their anti-AF efficacy in canine isolated arterially perfused right atria.


METHODS
Transmembrane action potentials and pseudoelectrocardiograms were recorded. Acetylcholine (ACh, 1.0 muM) was used to induce persistent AF.


RESULTS
Amiodarone-induced changes were much more pronounced than those of dronedarone on (1) action potential duration (DeltaAPD(90), +51 +/- 17 ms vs. 4 +/- 6 ms, P >.01), (2) effective refractory period (DeltaERP, +84 +/- 23 ms vs. 18 +/- 9 ms, P <.001), (3) diastolic threshold of excitation (DeltaDTE, +0.32 +/- 0.11 mA vs. 0.03 +/- 0.02 mA, P <.001), and (4) V(max) (DeltaV(max), -43 +/- 14% vs. -11 +/- 4%, P <.01, n = 5 to 6; all recorded at 10 muM, cycle length = 500 ms). Persistent AF was induced in 10 of 10 atria exposed to ACh alone; subsequent addition of dronedarone or amiodarone terminated AF in 1 of 7 and 4 of 5 atria, respectively. Persistent ACh-mediated AF was induced in 5 of 6 and 0 of 5 atria pretreated with dronedarone and amiodarone, respectively.


CONCLUSIONS
The electrophysiological effects and anti-AF efficacy of acute dronedarone are much weaker than those of amiodarone in a canine model of AF. The efficacy of acute dronedarone to prevent induction of acetylcholine-mediated AF as well as to terminate persistent AF in canine right atria is relatively poor. Our data suggest that acute dronedarone is a poor substitute for amiodarone for acute cardioversion of AF or prevention of AF recurrence.
Burashnikov
Alexander
A
Masonic Medical Research Laboratory, Utica, New York 13501, USA. sasha@mmrl.edu
Belardinelli
Luiz
L
Antzelevitch
Charles
C
D000638:Amiodarone / Q000008:administration & dosage* / Q000031:analogs & derivatives*; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000008:administration & dosage*; D001281:Atrial Fibrillation / Q000188:drug therapy / Q000503:physiopathology / Q000517:prevention & control*; D004195:Disease Models, Animal; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D000077764:Dronedarone; D022062:Electrophysiologic Techniques, Cardiac; D006325:Heart Atria / Q000187:drug effects* / Q000503:physiopathology; D006329:Heart Conduction System / Q000187:drug effects* / Q000503:physiopathology; D016896:Treatment Outcome
D000889:Anti-Arrhythmia Agents; D000077764:Dronedarone; D000638:Amiodarone