Principal Findings:

Upon admission to the hospital, patients in the EMERALD trial were randomized to one of five oral treatment arms—dofetilide at doses of 125 (n=135), 250 (n=133), or 500 (n=129) mcg BID; sotalol 80 mg BID (n=137); or placebo (n=137). Patients who did not convert with medical therapy by the third hospital day were electrically cardioverted. If successful, patients entered the one-year outpatient maintenance phase of the study.

After three days of treatment, 29.5% of patients in the 500 mcg dofetilide group and 10.5% in the 250 mcg group had converted to normal sinus rhythm (NSR) (p=0.001 vs. placebo for both arms), most within 24 hours of administration. The sotalol and low-dose dofetilide patients achieved a conversion rate of 5.9% and 5.1%, respectively. After cardioversion, more than 75% of patients in each treatment arm were in NSR and eligible for the maintenance phase.

At 3, 6, and 12 months, all doses of dofetilide maintained significantly more patients in NSR than placebo (p<0.005). High-dose dofetilide was significantly better than low-dose dofetilide and sotalol. For example, patients treated with high-dose dofetilide were more likely to remain in NSR at the end of one year (66%) compared to the placebo group (21%) or the sotalol group (50%).

Treatment was well tolerated, with the incidence of serious adverse events similar in all treatment groups. Discontinuation of therapy for a treatment-related event also was very low. Among the high-dose dofetilide group, there were four occurrences of torsade de pointes or other unfavorable arrhythmias. The incidence of minor adverse effects was evenly distributed among all treatment arms.