Beta-adrenergic blockade in chronic heart failure: principles, progress, and practice

Abstract

Prolonged activation of the sympathetic nervous system in patients with impaired ventricular function exerts adverse effects on the heart and circulation by a variety of mechanisms that are triggered by the interaction of norepinephrine and epinephrine with alpha1-, beta1-, and beta2-adrenergic receptors. Drugs that interfere with the actions of the sympathetic nervous system on alpha- and beta-receptors might be expected to antagonize these deleterious effects. beta1-receptor blockers have been shown to prevent and reverse many of the structural and functional changes that occur during the progression of heart failure, and beta2- and alpha1-receptor blockade seems to enhance the ability of beta1-blockers to prevent the toxic effects of catecholamines. In a large number of randomized, double-blind, placebo-controlled trials, long-term treatment of patients with chronic heart failure with beta-adrenergic blockers improves cardiac function, ameliorates symptoms, and reduces the risk of death and hospitalization. The nature and consistency of these benefits have led an increasing number of physicians to conclude that most patients with heart failure should be considered candidates for long-term treatment with these drugs. Analysis of these clinical trials has also raised the possibility that beta-blockers might differ from each other. Specifically, might agents that block alpha1-, betal-, and beta2-receptors be more effective and better tolerated that agents that act selectively on the beta1-receptor? This hypothesis is now being evaluated in a large-scale, long-term, international trial.