Hemodynamic and clinical effects of combined verapamil and propranolol therapy in angina pectoris

Because of their common negative chronotropic and inotropic effects, combined therapy of beta-adrenergic blocking drugs and calcium channel antagonists has long been feared to produce synergistic cardiodepressant effects. To evaluate whether such fears are justified when such therapy is used in patients with angina pectoris, five hemodynamic and clinical studies were reviewed. These studies indicated that in patients with preserved ventricular function treated with low or moderate doses of propranolol, verapamil produced little change in cardiac performance; this finding was not significantly different from the effects of verapamil in the absence of beta-blockade. In patients receiving large doses of propranolol, verapamil produced modest but significant cardiodepressant effects; these could be avoided by withdrawal of propranolol for 24 hours. Adverse reactions, when they occurred, were primarily hemodynamic rather than electrophysiologic.Short-term (48 hours) and long-term (4 weeks) randomized controlled trials, which objectively evaluated exercise tolerance in patients with angina pectoris, demonstrated that combined therapy of verapamil and propranolol was superior not only to placebo but also to either drug alone. In patients with preserved left ventricular function, the incidence of adverse effects with combined therapy was small (less than 10%) but increased to 25% in patients with poor left ventricular performance (ejection fraction less than 30%). Combined therapy of nifedipine and propranolol also produced adverse hemodynamic and clinical reactions.Combined therapy of beta-adrenergic and calcium channel antagonists can provide substantial clinical benefits for patients with angina pectoris who remain symptomatic with either agent used alone. Because adverse effects can occur, however, patients being considered for such treatment need to be carefully selected and observed.