Comparative effects of nadolol-digoxin combination therapy and digoxin monotherapy for chronic atrial fibrillation

Abstract

In some patients with chronic atrial fibrillation, treatment with digitalis alone may fail to produce a satisfactory decrease in heart rate at rest or during exercise or emotional stress. Findings of a few clinical studies suggest that β blockade in combination with digitalis therapy may be of benefit in these patients. In a randomized, double-blind, placebo-controlled, parallel-group, 8-week study of 32 patients with chronic atrial fibrillation, the effects of digoxin therapy alone were compared with a combination of digoxin and nadolol. Criteria for entry into the study included ventricular rate at rest ≥80/min or ≥120/ min with exercise, and serum digoxin levels within the therapeutic range. After digoxin dose titration to produce therapeutic levels, digoxin dosage remained constant throughout the balance of the study. After a 2-week, single-blind placebo lead-in period, patients were randomized to receive either digoxin plus placebo or a combination of digoxin and nadolol. The dose of nadolol/placebo was titrated from 20 to 120 mg daily as tolerated. Twentyfour hour ambulatory electrocardiographic (Holter) recordings, symptom-limited exercise treadmill tests and serum digoxin and nadolol levels were obtained at the end of the single and double-blind treatment periods. Comparing endpoint with baseline, results from Holter recordings showed that patients treated with a combination of digoxin and nadolol had significant (p < 0.001) decreases in 24 hour average (78 ± 4 to 63 ± 3), minimum 1 hour average (54 ± 3 to 47 ± 2) and maximum 1 hour average (123 ± 8 to 97 ± 4) ventricular rate while the corresponding ventricular rate changes in patients receiving digoxin therapy alone were small (average −80 ± 3 to 84 ± 4, minimum −50 ± 3 to 54 ± 2 and maximum −144 ± 5 to 149 ± 6). During exercise testing, patients given combination therapy had significant decreases in peak exercise ventricular rate (p < 0.002) and double-product (p < 0.001) compared with patients given digoxin alone. There were no significant changes in exercise duration in either group. Serum digoxin levels in the combination and digoxin alone groups were 0.75 ± 0.14 and 0.90 ± 0.08 ng/ml at baseline, respectively, and were not altered at the end of the study when values were 0.92 ± 0.13 and 0.80 ± 0.90 ng/ml, respectively. One patient receiving combination therapy was discontinued from the study because of dizziness. In patients with chronic atrial fibrillation, the combination of digoxin and nadolol was well tolerated and more effective than digoxin alone in controlling excessively rapid ventricular rates during exercise and upon ambulatory monitoring.