Acute and chronic pharmacodynamic interaction of verapamil and digoxin in atrial fibrillation.

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Abstract
The safety, efficacy and pharmacologic effect of combined verapamil and digoxin were studied in 10 patients with chronic atrial fibrillation. Heart rate recordings, treadmill exercise tests, physical examinations and serum digoxin concentrations during chronic digoxin therapy were compared with those after the acute administration of verapamil and 1, 2, 4, 6 and 10 wk after the addition of oral verapamil to digoxin therapy. After both i.v. and chronic oral verapamil administration, resting and exercise heart rates were significantly lower. Increasing serum concentrations correlated with increasing suppression of heart rate at rest and during exercise. The mean resting heart rate by 24-h ambulatory ECG decreased from 87 .+-. 9 beats/min to 72 .+-. 6 beats/min. The mean treadmill exercise heart rate decreased more markedly, from a mean of 151 .+-. 26 beats/min to 106 .+-. 22 beats/min (both P < 0.001). During chronic therapy, heart rate reductions were seen 1 wk after the addition of verapamil and were maintained without change for the duration of the trial. Blood pressures at rest and during exercise were unchanged. Cardiomegaly was present on the entry chest X-ray in 6 patients; after verapamil, heart size decreased in 3 and was unchanged in 1; 2 patients had transient congestive heart failure that responded to diuretics. Serum digoxin levels increased from a mean of 1.6 .+-. 0.4 ng/ml to 2.7 .+-. 0.9 ng/ml (P < 0.001) during verapamil. The increase was observed in 9 of 10 patients but was not related to clinical signs of digitalis excess and no episodes of asystole were seen on the serial 24-h ECG. Chronic oral administration of verapamil, 320 mg/day, resulted in mean verapamil concentrations of 130-280 ng/ml (mean interdose concentration 140 .+-. 41 ng/ml) with great intersubject and intrasubject variability. Verapamil is effective in further suppressing the ventricular response rate in atrial fibrillation when given in combination with digitalis and can serve as an adjunct to digitalis therapy in the chronic management of patients with atrial fibrillation.