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  •    Dronedarone compared to amiodarone in a randomized trial: Safety and efficacy
    Siva Soma, M.D., Allegheny General Hospital, Pittsburgh, PA.

    Amiodarone is one of the most common drugs used for maintenance of sinus rhythm (SR) in patients with atrial fibrillation (AF). Significant adverse effects including pulmonary, hepatic and thyroid toxicity cause drug discontinuation in many patients. Dronedarone, a non-iodinated benzofuran derivative has similar pharmacologic action as amiodarone but a better safety profile. Various trials including ATHENA [2] and ADONIS [3] have shown dronedarone to be more effective than placebo for maintenance of sinus rhythm in AF and in reducing cardiovascular events.  However the efficacy and safety benefit of dronedarone has never been directly compared with amiodarone, which is the standard therapy for maintenance of sinus rhythm in AF.

    DIONYSOS study is the first head to head comparison of dronedarone with amiodarone.  It is a randomized, double-blind, and parallel group multicenter study. A total of 504 patients with persistent AF (AF more than 72 hrs) were randomized to treatment with dronedarone (249) and amiodarone(255). A composite endpoint of efficacy (measured by recurrence of AF or discontinuation for lack of efficacy) and safety (measured by discontinuation for intolerance) was chosen in this study. This provides a good assessment of the benefit/risk ratio of both the drugs. The incidence of composite primary end point was 75.1% in dronedarone and 58.8% in amiodarone groups (p<0.001). This was mainly driven by the increased incidence of AF recurrence in dronedarone (63.5%) compared to amiodarone (42%).

    Premature discontinuation of the drug was less frequent with dronedarone (10.4%) than amiodarone (13.3%). A pre-specified safety endpoint which included a broad range of end-organ toxicities including thyroid, hepatic, pulmonary, neurological e.t.c., showed a trend towards better safety profile with dronedarone but was not statistically significant (39.3% in dronedarone and 44.5% in amiodarone; p=0.129).  This however reached statistical significance when GI related side effects were excluded.

    The relatively short follow-up period (~12 months) makes assessment of long term adverse effects difficult. This is important especially since long term efficacy of amiodarone is limited by its toxicity. The results of this study are similar to a recent meta analysis comparing the efficacy of dronedarone with amiodarone which concluded that the former was less efficacious but comparatively safer [4]. It would be interesting to see how the differences in safety and toxicity profile pans out in long term follow up.


    1. Le Heuzey JY, De Ferrari GM, Radzik D, Santini M, Zhu J, Davy JM. 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. J Cardiovasc Electrophysiol. 2010 Jun 1;21(6):597-605.

    2. Hohnloser SH, Crijns HJGM, van Eickels M, et al. Effect of dronedarone on cardiovascular events in atrial fibrillation. N Engl J Med 2009; 360:668-678.

    3. Singh BN, Connolly SJ, Crijns HJ, et al. Dronedarone for Maintenance of Sinus Rhythm in Atrial Fibrillation or Flutter. N Engl J Med 2007; 357:987-999.

    4. Piccini JP, Hasselblad V, Peterson ED, et al. Comparative efficacy of dronedarone and amiodarone for the maintenance of sinus rhythm in patients with atrial fibrillation. J Am Coll Cardiol 2009; 54:1089-1095.

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