β-adrenergic blockade in chronic heart failure: Principles, progress, and practice

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 α₁-, β₁-, and β₂-adrenergic receptors. Drugs that interfere with the actions of the sympathetic nervous system on α- and β-receptors might be expected to antagonize these deleterious effects. β₁-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 β₂- and α₁-receptor blockade seems to enhance the ability of β₁-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 β-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 β-blockers might differ from each other. Specifically, might agents that block α₁, β₁-, and β₂-receptors be more effective and better tolerated that agents that act selectively on the β₁- receptor? This hypothesis is now being evaluated in a large-scale, long- term, international trial.