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

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 na