Analysis from several clinical studies show dronedarone appears to be consistently safe and effective in maintaining normal sinusal rhythm and ventricular rate control in patients with cardiac arrhythmia
Paris, France
November 15, 2005
Dronedarone also shown to reduce hospitalizations in a post hoc analysis in patients with atrial fibrillation

Several analyses of the pivotal EURIDIS and ADONIS studies and the ERATO trial, presented at the Scientific Sessions 2005 of the American Heart Association (AHA) held in Dallas from November 13 to 16, showed that dronedarone the new investigational multichannel blocker anti-arrhythmic appears to be effective with favorable tolerability in patients with atrial fibrillation (AF), the most frequent form of cardiac rhythm disorder. 

In a post-hoc analysis of the EURIDIS and ADONIS trials conducted by Stefan Hohnloser MD, PhD, et al. Professor of Medicine, Department of Internal Medicine J.W. Goethe University, Frankfurt, Germany and member of the Steering Committee of the EURIDIS and ADONIS trials, and a subject of a poster presentation at AHA 2005, dronedarone was shown to reduce a combined endpoint of all-cause hospitalizations or deaths compared to placebo in patients with paroxysmal and persistent AF by 27% (p=0.01). “This potential clinical benefit of dronedarone when combined with consistent sinus rhythm maintenance, may provide an important new treatment approach for AF and it will be prospectively assessed in a large morbidity and mortality study in AF patients, the ATHENA trial” Professor Hohnloser said.

In a separate pre-specified EURIDIS and ADONIS analysis conducted by Bramah Singh, MD, PhD, et al. Professor of Medicine, Department of Medicine, Cardiology Division, UCLA Medical School and Chairman of the ADONIS trial Steering Committee, and described in an oral presentation delivered at AHA 2005, dronedarone was shown to lower the risk of first recurrence of AF by 25 % (p<0.0001) across three pre-specified subgroups of patients: recent need for cardioversion therapy, presence of structural heart disease or those with previous treatment with amiodarone. “Importantly in each of the three subgroups considered, dronedarone was consistently and uniformly more effective than placebo”, Professor Singh said.  

In another poster presentation of the Phase III study ERATO in patients with permanent AF delivered by Jean-Marc Davy M.D. et al (Arnaud de Villeneuve Hospital, Montpellier, France), dronedarone was found to provide additional rate control on top of standard therapies in patients not adequately controlled with their current treatments, which include beta-blockers, digitalis and calcium channel blockers. The study’s primary endpoint showed that dronedarone significantly reduced the mean 24 hour heart rate by 11.7 beats per minute (bpm) and maximal exercise ventricular rate by 24.5 bpm at day 14 versus baseline  (p<0.0001) while the placebo group showed no significant change compared to baseline.

In the EURIDIS and ADONIS trials, adverse events rates were generally comparable in both groups. There is no statistically significant difference over placebo in the occurrence of serious treatment emergent adverse events in the ERATO study. There was no evidence of proarrhythmia nor episodes of torsades de pointe in the dronedarone groups in the all EURODIS, ADONIS and ERATO trials program, during the studies’ periods.

“With the recent analyses of the ADONIS/ EURIDIS trials and now the ERATO study, dronedarone seems to be consistently effective and safe in patients with atrial fibrillation across the different studies and appears not to be associated with pro-arrhythmic events nor signs of organ toxicity”, noted Peter Kowey, MD, Professor of medicine and Clinical Pharmacology at Jefferson Medical College in Philadelphia, a member of the Steering Committee for the EURIDIS/ADONIS trials, and chief of the Division of Cardiovascular Diseases at the Lankenau Hospital Main Line Health System and President of the Main Line Health Heart Center. “It thus could provide a valuable new treatment alternative in the management of atrial fibrillation,” Dr Kowey said. 

About  Atrial Fibrillation
Atrial fibrillation is a common heart arrhythmia. More than 2 million Americans have this abnormal heart rhythm, which can cause palpitations, shortness of breath and fatigue. The condition is increasingly frequent with advancing age and is often caused by age-related changes in the heart or as a result of cardiovascular disease. Without appropriate management, atrial fibrillation can lead to serious complications such as stroke and congestive heart failure.

About dronedarone
Dronedarone is a novel multichannel blocker developed for the maintenance of sinus rhythm and ventricular rate control in patients with atrial fibrillation (AF). The submission dossier for dronedarone is currently under review with the FDA and the EMEA.

The EURIDIS (EURopean trial In atrial fibrillation or flutter patients receiving Dronedarone for the maintenance of Sinus rhythm) trial was conducted in 14 countries and 77 centres throughout Europe and involved a total of 612 patients. The ADONIS (American-Australian trial with DronedarONe In atrial fibrillation or flutter patients for the maintenance of Sinus rhythm) trial involved 625 patients in 115 centres in the US, Canada, Argentina, Australia and South Africa. EURIDIS and ADONIS were multi-centre, double-blind placebo controlled trials with a common protocol designed to assess the efficacy of dronedarone for the maintenance of normal sinus rhythm in patients with atrial fibrillation.

The ERATO (Efficacy and safety of dronedARone for The cOntrol of ventricular rate) trial is a multinational, multicentre, double-blind, randomized study in which two parallel groups of patients with permanent AF. The study was conducted in 35 centres across nine European countries and enrolled 174 patients with symptomatic permanent AF of at least 6 months.

 

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U.S. Contact
Tricia Geoghegan, 1-908-872-2464, tricia.geoghegan@sanofi-aventis.com.