DALLAS — The novel investigational antiarrhythmic agent dronedarone reduced by 27% the 1-year combined incidence of hospitalization or death compared with placebo in a large group of patients with paroxysmal or persistent atrial fibrillation, Dr. Stefan H. Hohnloser reported at the annual scientific sessions of the American Heart Association.
He presented a post hoc analysis of two pivotal phase III, double-blind, randomized trials totalling 1,237 patients with atrial fibrillation: EURIDIS (the European Trial in Atrial Fibrillation or Flutter Patients Receiving Dronedarone for the Maintenance of Sinus Rhythm) and ADONIS (the American-Australian-African Trial With Dronedarone in Atrial Fibrillation or Atrial Flutter Patients for the Maintenance of Sinus Rhythm).
In EURIDIS/ADONIS, the combined 1-year rate of all-cause hospitalization or mortality was 30.9% with placebo, compared with 22.8% in patients who received dronedarone at 400 mg b.i.d. The rate of death or hospitalization for a cardiovascular cause was 19.2% with placebo and 16.1% with dronedarone, added Dr. Hohnloser, professor of medicine and director of clinical electrophysiology at Johann Wolfgang Goethe University in Frankfurt am Main, Germany.
This potential clinical benefit—and Dr. Hohnloser stressed that “potential” needs to be emphasized because this was a post hoc analysis—distinguishes dronedarone from the various antiarrhythmic agents currently marketed for maintenance of sinus rhythm, all of which have been shadowed by safety concerns. In the previously reported primary efficacy outcomes in EURIDIS/ADONIS, the recurrent atrial fibrillation rate was cut by 22% and 28%, respectively, with dronedarone.
Dronedarone is an amiodarone derivative designed to provide the parent drug's efficacy without its toxicities. Sanofi-Aventis has applied to the Food and Drug Administration and to European authorities for marketing approval for dronedarone for maintenance of sinus rhythm and ventricular rate control in those patients with atrial fibrillation or flutter.
The potential reduction in morbidity and mortality noted with dronedarone in EURIDIS/ADONIS, coupled with new evidence presented at the AHA meeting that the drug is effective for rhythm control for rate control, and suggests the drug may provide an important new treatment approach in atrial fibrillation, he said.
Dr. Jean-Marc Davy reported that in the double-blind efficacy and safety of dronedarone for the control of ventricular rate (ERATO) trial, dronedarone provided additional rate control in patients not adequately controlled with standard agents including β-blockers, calcium channel blockers, and/or digitalis.
ERATO involved 174 patients with permanent atrial fibrillation and a baseline heart rate in excess of 80 beats per minute despite standard rate-control agents. They were randomized to dronedarone at 400 mg b.i.d. or placebo while continuing on their previous medications.
The primary study end point—heart rate as assessed by 24-hour Holter monitoring on day 14—was decreased by a mean of 11.7 beats per minute with dronedarone, compared with baseline, but it was unchanged in the placebo arm. Maximal exercise ventricular rate was reduced by 24.5 beats per minute in the dronedarone arm, added Dr. Davy, who is with Arnaud de Villeneuve Hospital in Montpellier, France.
Dr. Hohnloser and Dr. Davy are consultants to Sanofi-Aventis.