INTRODUCTION. Atrial fibrillation is a frequent cause of worsening of symptoms in patients with congestive heart failure. The drugs currently available for maintenance of sinus rhythm all have major side effects. METHODS. In 34 Danish coronary care units, 1518 patients with congestive heart failure and reduced left ventricular systolic function were randomized to receive either placebo or a new class III antiarrhythmic drug, dofetilide. The dose of dofetilide was adjusted according to the presence of atrial fibrillation, the length of the QT interval, and renal function. Patients were continuously monitored electrocardiographically for the first 3 days of the study. The primary end point was all-cause mortality and follow-up was for at least 1 year. RESULTS. In the dofetilide/placebo groups, 311/317 patients died (41%/42%). The hazard ratio for dofetilide treatment was 0.95 (95% confidence interval, 0.81-1.11). Treatment with dofetilide reduced worsening of heart failure significantly (hazard ratio, 0.75; 0.63-0.89). After 1 year, 61% of patients with atrial fibrillation at the start of the study had converted to sinus rhythm on dofetilide, vs. 33% in the placebo group. After conversion to sinus rhythm, 78%/43% of patients in the dofetilide/placebo groups remained in sinus rhythm for at least 1 year. There were 25 instances (3%) of torsade de pointes ventricular tachycardia in the dofetilide group and none in the placebo group. CONCLUSION. In patients with congestive heart failure, dofetilide can effectively convert atrial fibrillation to sinus rhythm and maintain sinus rhythm after conversion. Hospitalization for congestive heart failure is reduced. Dofetilide does not affect mortality. (c)2001 by CHF, Inc.