Copyright © 1995 by the European Society of Cardiology.
© 1995 The European Society of Cardiology
Neurohormonal activation and congestive heart failure: today's experience with ACE inhibitors and rationale for their use
Division of Cardiology, Department of Medicine, Östra University Hospital Göteborg, Sweden
Correspondence: Axel Sigurdsson MD, PhD, Division of Cardiology, Department of Medicine, Östia Hospital, 41685 Göteborg, Sweden
Treatment with angiotensin converting enzyme (ACE) inhibitors delays deterioration and improves survival in chronic congestive heart failure and left ventricular dysfunction. In two large placebo-controlled trials with survivors of acute myocardial infarction, but with left ventricular dysfunction, mortality was significantly lower in the ACE inhibitor arms, with risk reductions of 19% (with captopril) 27% (with ramipril). A study of left ventricular dysfunction in more than 4000 patients resulted in significantly fewer myocardial infarctions among patients given enalapril than in those receiving placebo, the risk reduction was 24%.
Knowledge of the degree of neurohormonal activation in patients with congestive heart failure (New York Heart Association [NYHA] Functional Class II-III) appears to be of major importance in determining the efficacy of A CE inhibition. Patients with plasma concentrations above normal show the greatest increase in survival when treated with ACE inhibitors compared to similarly treated patients with low or normal neurohormonal plasma levels as well as those treated with placebo or direct-acting vasodilators. In a study of 239 patients with NYHA Class IV heart failure, randomized to receive enalapril or placebo, mortality was significantly reduced in patients receiving enalapril who had plasma noradrenaline, adrenaline, angiotensin II, aldosterone, or a trial natriuretic peptide levels above median values. No significant differences in survival between groups were found in patients with hormone levels below the median. A study in 804 men with congestive heart failure who received either enalapril or hydralazine plus isosorbide dinitrate showed the greatest reduction in mortality after 2 years in enalapril treated patients with plasma noradrenaline levels >900 pg. ml–1 or plasma renin levels >16ng. ml–1. h–1. These results indicate that the main rationale for ACE inhibition in chronic congestive heart failure, in left ventricular dysfunction, and after myocardial infarction is the modulation of prolonged neurohormonal activation. Knowledge of this effect may provide the means to forestall disease progression and thus offer long-term treatment benefits.
Key Words: Congestive heart failure • neurohormonal activation • angiotensin converting enzyme inhibitors • left ventricular dysfunction • sympathetic nervous system • renin-angiotensin system • baroreceptors
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  A. R. Houghton, M. Harrison, and A. J. Cowley Haemodynamic, neurohumoral and exercise effects of losartan vs. captopril in chronic heart failure: results of an ELITE trial substudy Eur J Heart Fail, December 17, 1999; 1(4): 385 - 393. [Abstract] [Full Text] [PDF]
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