Relative efficacy of oral verapamil and digoxin alone and in combination for the treatment of patients with chronic atrial fibrillation

Abstract

1. The efficacy of verapamil alone, or in combination with digoxin, was compared with digoxin alone in eight patients with chronic atrial fibrillation in this double-blind placebo-controlled study. 2. After 2 weeks on each treatment regimen, heart rate at rest and during progressive load treadmill exercise, left ventricular function at rest and nocturnal heart rate were measured. 3. Oral verapamil alone at a dose of 80 mg three times daily, or 40 mg of verapamil three times daily in combination with 0.25 mg of digoxin daily, was superior to digoxin alone in doses associated with high serum digoxin concentrations (mean +/- SEM 1.6 +/- 0.3 micrograms/l). This superiority manifested as greater control of heart rate during work rates equivalent to regular daily activities, and was not associated with deterioration in left ventricular function or worsening nocturnal bradycardia. 4. We conclude that the treatment of choice in patients with chronic atrial fibrillation is either 80 mg of verapamil three times daily or 40 mg of verapamil three times daily in combination with digoxin.

The pharmacologic treatment of atrial fibrillation

“…Epstein and Rosing reported [126] that when oral verapamil was administered in association with oral quinidine, a serious hypotension may develop; however, in their three cases the reported patients had severe hypertrophic myocardiopathy, a disease characterized by marked sensitivity to vasodilation, which can be produced by verapamil in combination with quinidine [39]. Since gallopamil [46] and diltiazem [127,128] appear to be similar to verapamil from an electrophysiologic point of view, a combination of diltiazem and quinidine might be successfully utilized for AF conversion. This hypothesis requires clinical studies to be verified.…”

“…Thus, for some authors [46] this combination represents the treatment of choice in many patients with chronic AF.…”

The drug treatment of atrial fibrillation.

“…Firstly, the negatively inotropic effect of verapamil may offset the benefits from its negative chronotropic effects. This is unlikely to be important as the negative inotropism of verapamil is mild and studies of left ventricular ejection fraction have failed to demonstrate any effect (Pomfret et al, 1988). Secondly, as discussed earlier, the loss of effective atrial contraction in atrial fibrillation is particularly likely to be felt during exercise and although heart rate control may help it is unlikely to replace the beneficial effect of atrial systole.…”

“…Exercise tolerance however, was not consistently improved by treatment with verapamil and patients did not complain of less breathlessness when exercise induced tachycardia had been controlled (Channer et al, 1987;Lewis et al, 1988). Oxygen consumption, as a measure of work rate, has been shown to be lower in patients treated with verapamil alone and in combination with digoxin (Pomfret et al, 1988) and maximum exercise capacity has also been shown to be increased by this combination (Lang et al, 1983). However, in most studies there has been a failure to improve breathlessness and consistently increase effort tolerance in patients despite improved heart rate control.…”

“…Verapamil (80 mg three times a day) given as oral therapy is as effective as oral digoxin in lowering resting ventricular rate in patients with atrial fibrillation but is superior to digoxin in reducing exercise induced tachycardia (Lang et al, 1983;Pomfret et al, 1988). However, a reduction in diurnal maximum heart rate can also be achieved by simply doubling the dose of digoxin (Channer et al, 1987) or combining digoxin and verapamil in low dosage afl (40 mg three times daily) (Channer et al, 1987;Lewis et al, 1987;Pomfret et al, 1988). When ambulatory recordings are analysed, high dose digoxin increases nocturnal bradycardia and ventricular pauses, whereas digoxin and verapamil in combination causes less bradycardia (Channer et al, 1987).…”