title: Beneficial neurohormonal profile of spironolactone in severe congestive heart failure: results from the RALES neurohormonal substudy.
abstract: OBJECTIVE
  We sought to evaluate the effects of spironolactone on neurohormonal factors in patients with severe congestive heart failure (CHF).
  
  
  BACKGROUND
  In the Randomized ALdactone Evaluation Study (RALES), spironolactone, an aldosterone receptor antagonist, significantly reduced mortality in patients with severe CHF. However, the mechanism of action and neurohormonal impact of this therapy remain to be clarified.
  
  
  METHODS
  The effects of spironolactone (25 mg/day; n = 54) or placebo (n = 53) on plasma concentrations of the N-terminal portion of atrial natriuretic factor (N-proANF), brain natriuretic peptide (BNP), endothelin-1 (ET-1), norepinephrine (NE), angiotensin II (AII), and aldosterone were assessed in a subgroup of 107 patients (New York Heart Association functional class III to IV; mean ejection fraction 25%) at study entry and at three and six months.
  
  
  RESULTS
  Compared with the placebo group, plasma levels of BNP (-23% at 3 and 6 months; p = 0.004 and p = 0.05, respectively) and N-proANF (-19% at 3 months, p = 0.03; -16% at 6 months, p = 0.11) were decreased after spironolactone treatment. Over time, spironolactone did not modify the plasma levels of NE and ET-1. Angiotensin II increased significantly in the spironolactone group at three and six months (p = 0.003 and p = 0.001, respectively). As expected, a significant increase in aldosterone levels was observed over time in the spironolactone group (p = 0.001).
  
  
  CONCLUSIONS
  Spironolactone administration in patients with CHF has opposite effects on circulating levels of natriuretic peptides (which decrease) and aldosterone and AII (which increase). The reduction in natriuretic peptides might be related to changes in left ventricular diastolic filling pressure and/or compliance, whereas the increase in AII and aldosterone probably reflects activated feedback mechanisms. Further studies are needed to link these changes to the beneficial effects on survival and to determine whether the addition of an AII antagonist could be useful in this setting.
authors.affiliation: Division of Cardiology, University of Louvain, Avenue Hippocrate 10/2800, B-1200 Brussels, Belgium. rousseau@card.ucl.ac.be
authors.forename: Michel F
authors.initials: MF
authors.lastname: Rousseau
authors.forename: Olivier
authors.initials: O
authors.lastname: Gurné
authors.forename: Daniel
authors.initials: D
authors.lastname: Duprez
authors.forename: Walter
authors.initials: W
authors.lastname: Van Mieghem
authors.forename: Annie
authors.initials: A
authors.lastname: Robert
authors.forename: Sylvie
authors.initials: S
authors.lastname: Ahn
authors.forename: Laurence
authors.initials: L
authors.lastname: Galanti
authors.forename: Jean Marie
authors.initials: JM
authors.lastname: Ketelslegers
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000804:Angiotensin II / Q000097:blood*; D009320:Atrial Natriuretic Factor / Q000097:blood*; D019332:Endothelin-1 / Q000097:blood*; D005260:Female; D006333:Heart Failure / Q000097:blood / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D000451:Mineralocorticoid Receptor Antagonists / Q000494:pharmacology* / Q000627:therapeutic use; D020097:Natriuretic Peptide, Brain / Q000097:blood*; D013148:Spironolactone / Q000494:pharmacology* / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D019332:Endothelin-1; D000451:Mineralocorticoid Receptor Antagonists; D000804:Angiotensin II; D020097:Natriuretic Peptide, Brain; D013148:Spironolactone; D009320:Atrial Natriuretic Factor