Dronedarone in high-risk permanent atrial fibrillation

Dronedarone is a new anti-arrhythmic drug developed for the management of atrial fibrillation (AF) and in major trials like Euridis/Adonis and Athena has been shown to reduce AF recurrence, slow the ventricular rate and reduce cardiovascular outcomes and deaths in patients with paroxysmal and persistent AF.In the background of these studies, PALLAS trial was designed with the hypothesis that patients with high-risk permanent AF would similarly benefit from dronedarone.This trial included patients aged ≥65 years with permanent AF of ≥6 months duration and at least one risk factor.Patients were randomised to receive dronedarone (400 mg twice daily) or placebo and both the groups were well matched with clinical characteristics and risk factors which included coronary artery disease (CAD) (40.8% vs 41.2%), previous stroke or transient ischaemic attack (26.9% vs 28.3%), symptomatic heart failure (14.4% vs 14.8%), a left ventricular ejection fraction of 40% or less (21.3% vs 20.7%), peripheral arterial disease (PAD) (11.6% vs 13.2%); or the combination of an age of ≥75 years, hypertension, and diabetes (18.2% vs 17.1%).CHADS2 score of ≥2 was seen in 88.1% in the drug arm and 89.3% in the placebo arm.The first co primary outcome was stroke, myocardial infarction, systemic embolism, or death from cardiovascular causes.The second co primary outcome was unplanned hospitalisation for a cardiovascular cause or death.The trial was prematurely terminated for safety reasons after a year of enrolment when 3236 patients had undergone randomisation.The first co primary outcome occurred in 43 patients receiving dronedarone and 19 receiving placebo (hazard ratio, 2.29; 95% confidence interval [CI], 1.34-3.94;