Singh et al. (97) reviewed the clinical trials reported to date on the new antiarrhythmic drug developed for the treatment of AF. The authors summarized the DAFNE (Dronedarone Atrial Fibrillation Study after Electrical Cardioversion), EURIDIS (European Trial in Atrial Fibrillation or Flutter Patients Receiving Dronedarone for the Maintenance of Sinus Rhythm), ADONIS (American-Australian-African Trial with Dronedarone in Patients with Atrial Fibrillation or Atrial Flutter for the Maintenance of Sinus Rhythm), and ATHENA (A Trial with Dronedarone to Prevent Hospitalization or Death in Patients with Atrial Fibrillation) trials and noted a modest antiarrhythmic drug efficacy of dronedarone compared with other antiarrhythmic drugs and placebo. Patients administered dronedarone had a recurrence rate of AF or atrial flutter of 43% compared with 54% in patients on placebo (p < 0.0001), comparable to quinidine. In the DIONYSIS (Efficacy and Safety of Dronedarone versus Amiodarone for the Maintenance of Sinus Rhythm in Patients with Atrial Fibrillation) study, the composite endpoint of AF recurrence or premature drug discontinuation in patients on drug for at least 6 months was reached by 74% of patients on dronedarone versus 55% on amiodarone. Dronedarone was effective in reducing ventricular rate on AF compared with placebo. Dronedarone was found to increase mortality in the ANDROMEDA (European Trial of Dronedarone in Moderate to Severe Congestive Heart Failure) trial, in patients with moderate to severe CHF. This increased mortality rate appeared to be due largely to worsening of heart failure, predominately in those patients with recently decompensated heart failure. In contrast, in the ATHENA trial, in patients with compensated heart failure, there was a 24% reduction in combined risk of CV hospitalization and all-cause mortality compared with placebo at 21 months follow-up. The Food and Drug Administration approved dronedarone for treatment of AF/atrial flutter largely on the basis of the results of the ATHENA trial. The researchers note, however, that in a pooled analysis of these 6 studies, in a total of 6,771 patients, dronedarone treatment was not significantly different with respect to placebo in the incidence of all-cause mortality of CV hospitalization. With respect to side effects, dronedarone was noted in these studies to cause a slight increase in creatinine due to inhibition of renal tubular secretion. The main clinical side effects were diarrhea, nausea, and vomiting. Thus, the authors concluded that dronedarone was moderately effective in the treatment of AF/atrial flutter, it may reduce CV hospitalization and all-cause mortality, it had less toxicity than amiodarone, it should not be used in patients with decompensated heart failure, and it is most likely a second- or third-line agent. The researchers also noted that its high cost (as much as $9 per day) makes it uncertain if it will be cost effective compared with generic amiodarone.