In September 2009, the European Union approved dronedarone ‘in adult clinically stable patients with a history of, or current non-permanent atrial fibrillation (AF) to prevent recurrence of AF or to lower ventricular rate’.1 This was the first new oral anti-arrhythmic agent to be approved in more than 20 years if dofetilide, which was never marketed in Europe, is discounted. The failure of multiple anti-arrhythmic drug development programmes for the prevention of ventricular arrhythmias led to a new but uncharted approach, the introduction of a drug specifically and only for the management of AF. This is an important therapeutic arena, which had not been directly addressed previously.2 The marketing authorisation for dronedarone followed an extensive development programme involving six trials that enrolled over 7000 patients (table 1).3–9

A small dose-ranging study (DAFNE—Dronedarone Atrial Fibrillation Study after Electrical Cardioversion) had identified that the smallest dose tested (dronedarone 400 mg bid) was the most suitable dose for the suppression of AF recurrence.3 EURIDIS (European Trial in Atrial Fibrillation or Flutter Patients Receiving Dronedarone for the Maintenance of Sinus Rhythm) and ADONIS (American–Australian–African Trial with Dronedarone in Atrial Fibrillation or Flutter for the Maintenance of Sinus Rhythm) were pivotal trials that showed a significant reduction in the time to recurrence of AF (HR 0.75; 95% CI 0.65 to 0.87; p<0.0001).4 A trial against an active comparator (amiodarone) was required by European regulators, and the DIONYSOS trial (Randomised Double Blind Trial to Evaluate Efficacy and Safety of Dronedarone (400 mg bid) vs 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 Atrial Fibrillation) clearly demonstrated that dronedarone was not nearly as effective at preventing the recurrence of AF even if the endpoint was a …