Is activation of the sympathetic nervous system beneficial or detrimental to the patient with chronic heart failure? Lessons learned from clinical trials with beta-adrenergic agonists and antagonists.
The sympathetic nervous system is markedly activated in most patients with congestive heart failure, but it is not clear whether such activity is clinically beneficial (and should be enhanced) or detrimental (and should be blocked). Some insights into this question can be gained by reviewing the results of clinical trials with beta-adrenergic agonists and antagonists. Long-term treatment with agents that stimulate the beta-receptor (prenalterol and pirbuterol) has not proved to be useful in the treatment of chronic heart failure; moreover, prolonged treatment with beta-agonists (dobutamine and pirbuterol) may adversely affect survival. Most of the studies with beta-agonists, however, have employed agents that interact nonselectively and with a high degree of intrinsic activity with both beta 1-and beta 2-receptors. It is possible that the problems that have been encountered with the use of beta-agonists could be minimized by agents that are more selective and have less intrinsic activity. Yet, such agents may actually function as beta-adrenergic antagonists (rather than agonists) in states of heightened sympathetic activity. Indeed, sustained therapy with drugs that attenuate the effects of the sympathetic nervous system (by blocking tyrosine hydroxylase or beta-adrenergic receptors) may produce hemodynamic and clinical improvement and may reduce long-term mortality in chronic heart failure. Although beta-adrenergic blockade carries important risks, these might be minimized by the use of drugs that spare myocardial and vascular beta 2-receptors or possess some intrinsic agonist activity.(ABSTRACT TRUNCATED AT 250 WORDS)
Packer
M
M
Department of Medicine, Mount Sinai School of Medicine, City University of New York, New York 10029.
D000318:Adrenergic beta-Agonists / Q000494:pharmacology / Q000627:therapeutic use*; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology / Q000627:therapeutic use*; D002908:Chronic Disease; D006333:Heart Failure / Q000188:drug therapy* / Q000503:physiopathology; D006801:Humans; D013564:Sympathetic Nervous System / Q000503:physiopathology*
D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists