Low- and medium-dose diltiazem in chronic atrial fibrillation: Comparison with digoxin and correlation with drug plasma levels

Abstract

The safety and efficacy of diltiazem were compared with digoxin maintenance therapy for control of ventricular response in 19 patients with chronic atrial fibrillation. The relationship between drug plasma levels and cardiovascular effects was also investigated. After 7 days of combined therapy with diltiazem (60 mg three times a day in 10 patients and four times a day in nine patients) and digoxin (0.125 mg/day in two patients and 0.250 mg/day in 17 patients), the 24-hour mean heart rate derived from ambulatory ECG recording was reduced by 16.3% in comparison with digoxin therapy alone; the serum digoxin level was not significantly changed (1.06 ± 0.43 vs 1.05 ± 0.61 ng/ml). After a standardized bicycle exercise test (50 watts for 3 minutes), maximal heart rate was reduced by 19.9%, diastolic blood pressure was decreased by 8.9%, and systolic pressure-rate product was decreased by 12.5%. Diltiazem plasma levels (mean 120.9 ± 63.3 ng/ml) were linearly correlated with percentage variations in maximal heart rate, diastolic blood pressure, systolic blood pressure, and pressure-rate product during exercise. Eighteen patients in succession discontinued digoxin therapy; after 14 days of diltiazem alone, the 24-hour mean heart rate returned to control values of digoxin therapy, whereas maximal heart rate and pressure-rate product during exercise were significantly reduced (−17.2% and −14.1%, respectively), with no changes in blood pressure. Diltiazem plasma levels (135.0 ± 83.2 ng/ml) showed a linear correlation with the percentage of reduction in maximal heart rate. There were no differences in mean diltiazem plasma levels between patients treated with 180 mg or 240 mg daily doses (131.0 ± 75.0 vs 125.6 ± 70.2 ng/ml, respectively). Thus diltiazem, at the doses used in the present study, was effective in the control of resting and exercise-induced ventricular responses in patients with chronic atrial fibrillation. Moreover, combined therapy with digoxin was superior for control of 24-hour mean heart rate as compared with each drug separately, with no risk of increased digoxin serum levels. The reduction in heart rate during exercise was linearly related to the plasma diltiazem level.