The Role of Vasodilator Therapy in the Treatment of Severe Chronic Heart Failure

M. Packer

Research output: Contribution to journalArticle

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Abstract

The rationale for the use of vasodilating agents in the treatment of congestive heart failure is to reverse the systemic vasoconstriction that characterises patients with this disorder, and which may further limit cardiac performance. Nitrates were the first vasodilators used, followed by arterial vasodilators (hydralazine, minoxidil), α-adrenergic blockers (prazosin, trimazosin) and, more recently, calcium antagonists, ACE inhibitors, β-agonists and phosphodiesterase inhibitors. The choice of vasodilator should be based on consideration of overall benefit-risk profiles. Consideration of pharmacological action together with classification of patients into haemodynamic subsets has been used as a basis from which to initiate vasodilator therapy. However, such a classification may not lead to a logical choice of drug and there is no evidence to suggest that patients so selected do better when given long term treatment with peripherally specific drugs than with agents that are not tailored to pretreatment haemodynamic variables. Moreover, changes in central haemodynamics after administration of specific vasodilator drugs may differ from those expected on the basis of their presumed actions on the peripheral vasculature. Dosage requirements are difficult to predict with many vasodilator drugs. Traditionally, such requirements have been established by titrating vasodilating drugs to achieve an arbitrarily defined haemodynamic response. However, there is little correlation between haemodynamic end-points and clinical efficacy in patients with heart failure, and short and long term haemodynamic responses to vasodilator drugs are not necessarily related. Drug-specific haemodynamic and clinical tolerance occurs during the course of treatment with all vasodilator drugs; the extent and frequency with which it develops differs between agents. Tolerance is thought to arise from a reduction in drug receptor affinity and/or density or activation of counter-regulatory forces (mainly neurohormonal) that limit the magnitude of vasodilatation that can be achieved. Development of tolerance to a single agent does not usually preclude efficacy of other agents. ACE inhibitors have been associated with a relatively low incidence of tolerance. This may relate to their natriuretic effect and ability to decrease the degree of neurohormonal activation, actions not shared by other vasodilators. Tolerance is the principal reason for failure of prazosin and nitrates as therapeutic agents in severe chronic heart failure. Side effects inherent in all vasodilator drugs include hypoperfusion reactions (symptomatic hypotension, renal insufficiency) and those related to secondary activation of the sympathetic nervous and renin-angiotensin systems (tachycardia, fluid retention, myocardial ischaemia). Compared with other vasodilators, ACE inhibitors are more likely to produce hypoperfusion reactions but less likely to cause side effects related to neurohormonal activation. Because of the poor prognosis for severe chronic heart failure, concerns about the occurrence of adverse drug reactions during long term use of some vasodilators (lupus syndrome and hydralazine) should not preclude use or necessitate discontinuation of effective therapy. The prognosis for heart failure appears to be primarily determined by neurohormonal factors; circulating levels of noradrenaline and angiotensin II are most elevated in patients with the least favourable long term prognosis. Vasodilators such as the ACE inhibitors and β-blockers which modify the neurohormonal response in chronic heart failure may thus be expected to achieve a favourable impact on survival. Large scale trials are currently in progress to prospectively address this issue.

Original languageEnglish (US)
Pages (from-to)13-26
Number of pages14
JournalDrugs
Volume32
Issue number5
DOIs
StatePublished - Dec 1986

ASJC Scopus subject areas

  • Pharmacology (medical)

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