Dronedarone is effective and well-tolerated in the prevention of atrial fibrillation

Aug 29 2004

The findings of the “American-Australian-African trial with DronedarONe In atrial fibrillation or flutter patients for the maintenance of Sinus rhythm” (ADONIS) trial, announced at the annual meeting of the European Society of Cardiology in Munich, Germany showed that the new anti-arrhythmic agent, dronedarone, is highly effective in the prevention of atrial fibrillation or atrial flutter recurrence, serious disorders of cardiac rhythm, and is well-tolerated by patients.

ADONIS is part of the clinical investigation program on the novel multi-channel blocker, dronedarone, in this patient population, which also includes the European trial EURIDIS (EURopean trial In atrial fibrillation or flutter patients receiving Dronedarone for the maIntenance of Sinus rhythm).

The ADONIS trial involved 625 patients in 115 centers in the US, Canada, Argentina, Australia and South Africa. The study compared the efficacy and safety of dronedarone to placebo in patients who had already had at least one ECG-documented atrial fibrillation or flutter in the three month period prior to randomization and who were in sinus rhythm for at least one hour at the time of randomization. Using 2:1 randomization in order to optimize the assessment of safety parameters, patients received either 400 mg bid of dronedarone (n=417) or placebo (n=208) for a period of 12 months. The primary endpoint of ADONIS was the time from randomization to the first adjudicated recurrence of atrial fibrillation or flutter (AF/AFL) within the 12 month study period. All recurrences of AF/AFL had to last for at least ten minutes and were confirmed by two consecutive electrocardiograms (ECGs) or Trans-Telephonic Electrocardiographic Monitoring (TTEM) tracings recorded approximately 10 minutes apart and both showing atrial fibrillation or flutter.

“ADONIS demonstrated that dronedarone is a highly effective and well tolerated agent in the prevention of both symptomatic and asymptomatic recurrences of AF/AFL,” said Bramah N. Singh, MD, PhD, Professor of Medicine, Department of Medicine, Cardiology Division, UCLA Medical School and Chairman of the ADONIS trial Steering Committee. “Dronedarone was also shown to be effective in decreasing the heart rate of patients with AF recurrences and the drug’s cardiac tolerability was good with no cases of torsades de pointes,” he added.

The ADONIS study showed that the median time from randomization to a first adjudicated AF/AFL recurrence was 2.7-fold longer in the dronedarone group than in the placebo group. Dronedarone significantly decreased the risk of a first recurrence of AF/AFL within the 12-month study period by 27.5% compared to placebo (log-rank test p=0.0017).

Most initial AF/AFL recurrences were symptomatic in both groups of patients. Overall incidence of adverse events was comparable in the two groups (73% in the placebo arm and 80% in the dronedarone group, (p = ns)) and dronedarone also displayed good cardiac tolerability, with no cases of torsades de pointes.

“The results of the ADONIS and EURIDIS trials show remarkable consistency for both the antiarrhythmic efficacy as well as the safety of dronedarone,” said Stefan Hohnloser MD, PhD, Professor of Medicine, Department of Internal Medicine J.W. Goethe University, Frankfurt, Germany and member of the EURIDIS trial Steering Committee. “Given the relatively poor benefit-to-risk ratios of currently available anti-arrhythmic therapies, the results of the EURIDIS and ADONIS trials appear to position dronedarone as a promising option for cardiac rhythm space and rate control in atrial fibrillation,” he added.