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 μM) was used to induce persistent AF. Results: Amiodarone-induced changes were much more pronounced than those of dronedarone on (1) action potential duration (ΔAPD₉₀, +51 ± 17 ms vs. 4 ± 6 ms, P >.01), (2) effective refractory period (ΔERP, +84 ± 23 ms vs. 18 ± 9 ms, P <.001), (3) diastolic threshold of excitation (ΔDTE, +0.32 ± 0.11 mA vs. 0.03 ± 0.02 mA, P <.001), and (4) V_max (ΔV_max, −43 ± 14% vs. −11 ± 4%, P <.01, n = 5 to 6; all recorded at 10 μM, 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. Conclusion: 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. [Copyright &y& Elsevier]