In the treatment of heart failure and atrial fibrillation, digoxin has been a longstanding option. It is standard therapy in patients with heart failure and atrial fibrillation, but it is inadequate at rate control in these patients during exercise or times of increased sympathetic tone. Multiple studies have shown the benefit of beta-blocker therapy in the treatment of patients with heart failure. In addition, beta blockers have been shown to improve ventricular rate control in atrial fibrillation alone or in combination with digoxin. Despite these studies, no information demonstrates that beta blockers alone or in combination with digoxin improve outcomes in patients with heart failure and persistent atrial fibrillation. Khand and associates evaluated the use of digoxin, carvedilol, and their combination in the treatment of patients with heart failure and persistent atrial fibrillation.
The trial was a randomized, double-blind, placebo-controlled study of patients who met the standard criteria for heart failure and persistent atrial fibrillation for more then one month. All patients who entered the trial were taking digoxin. In phase 1 of the study, digoxin alone was compared with the combination of carvedilol and digoxin for four months. In phase 2, digoxin was withdrawn in a double-blinded fashion. Patients were assessed at the start of the study and at the end of each phase. Primary outcome measurements included assessment of left ventricular function, ventricular rate control, symptoms, and exercise tolerance.
There were 47 patients who participated in the study. The combination of digoxin and carvedilol, when compared with digoxin alone, provided a significantly lower ventricular rate on 24-hour monitoring and during submaximal exercise. In addition, combination therapy provided significantly better symptom control and improved left ventricular function compared with digoxin alone. When patients were changed to carvedilol alone, their mean ventricular rate rose, and the left ventricular ejection fraction declined. There was no difference in the six-minute walk distance between treatment arms.
The authors conclude that the combination of digoxin and carvedilol in the treatment of patients with heart failure and persistent atrial fibrillation is superior to either medication alone. They add that the combination provides better left ventricular function and ventricular rate control. In patients who were taking the combination, left ventricular function and rate control deteriorated after digoxin withdrawal. This study is the first to demonstrate the added benefit of digoxin in patients who are receiving beta-blocker therapy.