Effect of Corwin (ICI 118587) on resting and exercise heart rate and exercise tolerance in digitalised patients with chronic atrial fibrillation.

Abstract

The effect of Corwin, a new oral beta, partial agonist, on the ventricular response to atrial fibrillation was studied in digitalised patients during 24 hour ambulatory electrocardiography and during exercise on a treadmill in a double blind placebo controlled crossover trial. Corwin reduced the maximum heart rate during exercise from 162(16) beats/min to 120(9) beats/min and reduced the peak heart rate during ambulatory electrocardiography from 113(11) to 90(6) beats/min consistent with a beta adrenoreceptor antagonist action at higher levels of sympathetic nervous system activity. Minimum heart rate during ambulatory electrocardiography was increased from 62(5) to 70(5) beats/min indicating that at lower levels of sympathetic activity the drug acts as a beta agonist. The drug increased exercise tolerance significantly. Serum digoxin concentrations were not affected by the drug. Thus Corwin appears to be effective in stabilising heart rate during atrial fibrillation both at rest and during exercise in digitalised patients.

Predominantβ-adrenoceptor blocking effect of xamoterol averaged over the day in patients with mild to moderate heart failure: insight into the mechanism of its long-term clinical efficacy

“…Therefore, its overall effect is to stabilise sympathetic control of the heart at a level equal to the PAA [1]. In the clinical setting the stabilising effect has been characterised by a reduction in the circadian variability of heart rate [19,20]. However, conventional analysis of mean hourly heart rate is not necessarily useful for quantification of the net chronotropic effect on the diurnal average, although it can clearly illustrate the circadian prone of the effect of a drug.…”

Chronic atrial fibrillation: a systematic review of medical heart rate control management

“…However, the effect of this combination on exercise tolerance is inconsistent, with some studies reporting deterioration in exercise capacity,31–33 35 41 some improvement26 36 39 and most no change 22 24 27 28 31 34 37 40 42 44…”

“…The combination of xamoterol with digoxin resulted in improved exercise tolerance and also less HR variability compared with digoxin alone. Digoxin and xamoterol were used in combination in three double-blind, randomised, cross-over studies 31 34 36. Molajo et al found that this combination improved exercise tolerance and 24 h HR variability,36 but the other two reported unchanged exercise tolerance compared with digoxin.…”

The drug treatment of atrial fibrillation.

“…Another ,B-adrenoceptor partial agonist, xamoterol, has also been shown to be effective at controlling ventricular rate in patients with atrial fibrillation (Molajo et al, 1984). Xamoterol has positive inotropic effects (James et al, 1990) and can be used in the treatment of mild heart failure (German & Austrian Xamoterol Study, 1988), it therefore offers considerable advantages over adjuvant treatment with ,B-adrenoceptor blockers in atrial fibrillation.…”

“…Xamoterol has positive inotropic effects (James et al, 1990) and can be used in the treatment of mild heart failure (German & Austrian Xamoterol Study, 1988), it therefore offers considerable advantages over adjuvant treatment with ,B-adrenoceptor blockers in atrial fibrillation. In a double-blind cross over study additional treatment with xamoterol 200 mg twice daily to digitalised patients reduced maximum diurnal and exercise induced heart rate, increased minimal heart rate and prolonged exercise tolerance (Molajo et al, 1984). In a more recent placebo controlled study xamoterol was given to patients with atrial fibrillation and excessive bradycardia (Ang et al, 1990).…”