Rhythm- and rate-controlling effects of dronedarone in patients with atrial fibrillation (from the ATHENA trial)

Abstract

Dronedarone is a multi-channel-blocking drug for the treatment of patients with atrial fibrillation (AF) or atrial flutter (AFL) with rate- and rhythm-controlling properties. A Placebo-Controlled, Double-Blind, Parallel Arm Trial to Assess the Efficacy of Dronedarone 400 mg b.i.d. for the Prevention of Cardiovascular Hospitalization or Death from Any Cause in Patients With Atrial Fibrillation/Atrial Flutter (ATHENA) demonstrated that dronedarone reduced the risk for first cardiovascular hospitalization or death from any cause. The aim of this post hoc analysis was to evaluate the rhythm- and rate-controlling properties of dronedarone in the ATHENA trial. Patients were randomized to dronedarone 400 mg twice daily (n = 2,301) or placebo (n = 2,327). Electrocardiographic tracings were classified for AF or AFL or sinus rhythm. Patients with AF or AFL on every postbaseline electrocardiogram were classified as having permanent AF or AFL. All electrical cardioversions were documented. The use of rate-controlling medications was equally distributed in the 2 treatment groups. The median time to first AF or AFL recurrence of patients in sinus rhythm at baseline was 498 days in placebo patients and 737 days in dronedarone patients (hazard ratio 0.749, 95% confidence interval 0.681 to 0.824, p <0.001). In the dronedarone group, 339 patients (15%) had ≥1 electrical cardioversion, compared to 481 (21%) in the placebo group (hazard ratio 0.684, 95% confidence interval 0.596 to 0.786, p <0.001). The likelihood of permanent AF or AFL was lower with dronedarone (178 patients [7.6%]) compared to placebo (295 patients [12.8%]) (p <0.001). At the time of first AF or AFL recurrence, the mean heart rates were 85.3 and 95.5 beats/min in the dronedarone and placebo groups, respectively (p <0.001). In conclusion, dronedarone demonstrated both rhythm- and rate-controlling properties in ATHENA. These effects are likely to contribute to the reduction of important clinical outcomes observed in this trial.

Trial registration: ClinicalTrials.gov NCT00174785.