A Short-term, Randomized, Double-Blind, Parallel-group Study to Evaluate the Efficacy and Safety of Dronedarone versus Amiodarone in Patients with Persistent Atrial Fibrillation: The DIONYSOS Study

Jean-Yves Le Heuzey, M.D.; Gaetano M. De Ferrari, M.D.; David Radzik, M.D.; Massimo Santini, M.D.; Junren Zhu, M.D.; Jean-Marc Davy, M.D.

Disclosures

J Cardiovasc Electrophysiol. 2010;21(6):606-607. 

In This Article

Abstract and Introduction

Abstract

Dronedarone versus Amiodarone in Patients with AF. Introduction: We compared the efficacy and safety of amiodarone and dronedarone in patients with persistent atrial fibrillation (AF).
Methods: Five hundred and four amiodarone-naïve patients were randomized to receive dronedarone 400 mg bid (n = 249) or amiodarone 600 mg qd for 28 days then 200 mg qd (n = 255) for at least 6 months. Primary composite endpoint was recurrence of AF (including unsuccessful electrical cardioversion, no spontaneous conversion and no electrical cardioversion) or premature study discontinuation. Main safety endpoint (MSE) was occurrence of thyroid-, hepatic-, pulmonary-, neurologic-, skin-, eye-, or gastrointestinal-specific events, or premature study drug discontinuation following an adverse event.
Results: Median treatment duration was 7 months. The primary composite endpoint was 75.1 and 58.8% with dronedarone and amiodarone, respectively, at 12 months (hazard ratio [HR] 1.59; 95% confidence interval [CI] 1.28–1.98; P < 0.0001), mainly driven by AF recurrence with dronedarone compared with amiodarone (63.5 vs 42.0%). AF recurrence after successful cardioversion was 36.5 and 24.3% with dronedarone and amiodarone, respectively. Premature drug discontinuation tended to be less frequent with dronedarone (10.4 vs 13.3%). MSE was 39.3 and 44.5% with dronedarone and amiodarone, respectively, at 12 months (HR = 0.80; 95% CI 0.60–1.07; P = 0.129), and mainly driven by fewer thyroid, neurologic, skin, and ocular events in the dronedarone group.
Conclusion: In this short-term study, dronedarone was less effective than amiodarone in decreasing AF recurrence, but had a better safety profile, specifically with regard to thyroid and neurologic events and a lack of interaction with oral anticoagulants.

Introduction

Atrial fibrillation (AF) is a major cause of morbidity, increasing the risk of stroke and death, and remains a significant health concern.[1,2] Amiodarone is widely used for the maintenance of sinus rhythm in patients with AF; however, it is associated with adverse events, such as pulmonary toxicity, thyroid disorders, and hepatic toxicity, that can lead to drug discontinuation and/or serious complications during long-term treatment.[3–5]

Dronedarone is a noniodinated benzofuran derivative that is pharmacologically related to amiodarone but with significant molecular differences leading to different relative effects on individual ion channels and an improved pharmacokinetic profile (shorter half-life and reduced accumulation in tissues).[6–9,10] This improved pharmacokinetic profile may account for the absence of amiodarone-like organ toxicity observed with dronedarone in AF clinical trials.[11–14] Dronedarone has demonstrated efficacy in the treatment of arrhythmia in terms of prevention of AF recurrences.[11,12] Furthermore, in contrast with amiodarone, dronedarone has been shown to significantly reduce hard endpoints among patients with AF in the ATHENA (A Placebo-Controlled, Double-Blind, Parallel Arm Trial to Assess the Efficacy of Dronedarone 400 mg bid for the Prevention of Cardiovascular Hospitalization or Death from Any Cause in patiENts with Atrial Fibrillation/Atrial Flutter) trial.[14]

DIONYSOS (Randomized, Double-Blind TrIal to Evaluate the Efficacy and Safety of DrOnedarone [400 mg bid] Versus AmiodaroNe [600 mg qd for 28 daYS, then 200 mg qd Thereafter] for at Least 6 mOnths for the Maintenance of Sinus Rhythm in Patients with AF) is a short-term study comparing dronedarone and amiodarone. This study was conducted following recommendations from the European Authorities to provide elements of comparison of the benefit risk ratio of dronedarone with respect to a marketed and widely used agent for the treatment of AF, amiodarone. Knowing that amiodarone is effective for the prevention of AF recurrences but is often discontinued for side effects, some of which can be severe, the study was designed to take into account efficacy and safety aspects, particularly in the definition of the primary endpoint.

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