Although heart failure has been viewed primarily as a haemodynamic disorder, the development of pharmacologic agents that address the haemodynamic derangements has not proved to be a successful approach to its management. Consequently, attention in recent years has shifted to the development of neurohormonal antagonists in the hope that prolonged interference with the renin-angiotensin system and the sympathetic nervous system would have favourable effects on the natural history of heart failure. Both converting-enzyme inhibitors and beta-adrenergic blockers have been shown to produce long-term haemodynamic and clinical benefits in patients with left ventricular systolic dysfunction in controlled clinical trials. For both classes of drugs, the improvement evolves gradually over several months, although initiation of therapy may be accompanied by undesirable (but usually transient) haemodynamic effects. This pattern of response contrasts sharply with the response pattern seen with direct-acting vasodilators that stimulate neurohormonal systems (e.g. flosequinan). Initiation of treatment with flosequinan produces immediate clinical benefits due to the haemodynamic actions of the drug, but this improvement may disappear within weeks as a result of neurohormonal activation, which also may contribute to the increased risk of death seen during long-term administration of the drug. Recognition of the prognostic importance of neurohormonal activation has led to the hope that long-term treatment with beta-blockers might reduce mortality in heart failure, in a manner similar to that seen with converting-enzyme inhibitors. Large-scale, long-term studies are being planned to evaluate this possibility.
- Clinical trials
- Heart failure
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine