Modulation of functional capacity and survival in congestive heart failure. Effects of activation of the sympathetic nervous system.

Although the sympathetic nervous system is markedly activated in most patients with congestive heart failure, it is not clear whether such activity is clinically beneficial (and should be reinforced) or detrimental (and should be pharmacologically blocked). Some insights pertinent to this important question can be gained by reviewing the results of clinical trials with beta agonists and antagonists. Neither beta 1-selective (prenalterol) nor beta 2-selective (pirbuterol) agonists have been shown to be effective in treating heart failure in double-blind, placebo-controlled studies; moreover, research has indicated that prolonged stimulation of beta receptors with oral or intravenous catecholamines may adversely affect survival. In contrast, sustained therapy with drugs that attenuate the effects of the sympathetic nervous system (by blocking either tyrosine hydroxylase or beta-adrenergic receptors) may produce hemodynamic and clinical improvement and may favorably affect long-term prognosis. These potential benefits of beta-adrenergic blockade contrast strikingly with the lack of efficacy (with respect to clinical status and survival) of agents that block alpha-adrenergic receptors. Beta-adrenergic blockade carries important risks in the patient with heart failure, however. The risk-to-benefit ratio cannot be delineated accurately until the outcome of additional randomized clinical trials is known.