A double blind placebo controlled comparison of verapamil, atenolol, and their combination in patients with chronic stable angina pectoris.

Abstract

SUMMARY The efficacy and effect on cardiac function of verapamil 120 mg three times a day and atenolol 100mg once a day, singly and in combination, were evaluated in 15 patients with angina pectoris. While they were on the combination treatment four patients withdrew from the study. Episodes of angina pectoris and glyceryl trinitrate consumption were significantly reduced only on the combination. On the combination only four patients developed evidence of ischaemia during exercise compared with seven on verapamil and ten on atenolol. ST segment depression at peak exercise, assessed by 16 point precordial mapping, was reduced by all active treatments from 7 1 on placebo to 2-7, 0-9, and 0-6 mm on atenolol, verapamil, and the combination respectively. Mean left ventricular ejection fraction fell significantly from 60% on placebo to 53% on the combination but was unchanged on verapamil and atenolol.

Evaluation of potential pharmacodynamic and pharmacokinetic interactions between verapamil and propranolol in normal subjects.

“…Previous studies of potential pharmacokinetic interference between verapamil and ,-adrenoceptor antagonists have produced conflicting results. No interaction was reported after repeated doses of verapamil, propranolol, metoprolol and atenolol in normals (Warrington et al, 1984) or between verapamil and atenolol in patients with angina (Findlay et al, 1987;Keech et al, 1986). However, increased plasma concentrations of the lipid-soluble ,3-adrenoceptor antagonists metoprolol (Keech et al, 1986;McLean et al, 1985) and propranolol (McGourty et al, 1988) were noted after repeated dosing in combination with verapamil.…”

“…The degree of 13-adrenoceptor antagonism has been considered critical in the develop-ment of adverse cardiac events (Packer et al, 1982b) because dampening of ,B-adrenergic reflexes may allow the cardiodepressant effect of verapamil to predominate. However, the variability in reported incidence of detrimental reactions (Findlay et al, 1987;McInnes et al, 1986) may reflect differences between study populations in cardiac reserve and sinus node function as much as in the extent of ,B-adrenoceptor blockade.…”

??-Blockers Drug Interactions of Clinical Significance

“…There are reports of hypotension, haemodynamically significant bradycardia and heart failure, as well as haemodynamic collapse associated with the concurrent use of verapamil and ~-blockade. [24][25][26][27] Marked bradycardia has even been described in patients receiving timolol eye drops and oral verapamil. [28,29] In terms of pharmacokinetic interactions, there are conflicting reports.…”

High Blood Pressure and Calcium Antagonism

“…These effects, thus, counteract the initially beneficial haemody namic effects of nifedipine [39][40][41][42]. Reflex tachycardia is less marked with diltiazem, and slight bradycardia is usually seen with verapamil due to its direct action on sin us node discharge [43].…”