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Beneficial neurohormonal profile of spironolactone in severe congestive heart failure: results from the RALES neurohormonal substudy.
J Am Coll Cardiol. 2002 Nov 06; 40(9):1596-601.JACC

Abstract

OBJECTIVES

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+Show Affiliations

Division of Cardiology, University of Louvain, Avenue Hippocrate 10/2800, B-1200 Brussels, Belgium. rousseau@card.ucl.ac.beNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Clinical Trial
Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

12427411

Citation

Rousseau, Michel F., et al. "Beneficial Neurohormonal Profile of Spironolactone in Severe Congestive Heart Failure: Results From the RALES Neurohormonal Substudy." Journal of the American College of Cardiology, vol. 40, no. 9, 2002, pp. 1596-601.
Rousseau MF, Gurné O, Duprez D, et al. Beneficial neurohormonal profile of spironolactone in severe congestive heart failure: results from the RALES neurohormonal substudy. J Am Coll Cardiol. 2002;40(9):1596-601.
Rousseau, M. F., Gurné, O., Duprez, D., Van Mieghem, W., Robert, A., Ahn, S., Galanti, L., & Ketelslegers, J. M. (2002). Beneficial neurohormonal profile of spironolactone in severe congestive heart failure: results from the RALES neurohormonal substudy. Journal of the American College of Cardiology, 40(9), 1596-601.
Rousseau MF, et al. Beneficial Neurohormonal Profile of Spironolactone in Severe Congestive Heart Failure: Results From the RALES Neurohormonal Substudy. J Am Coll Cardiol. 2002 Nov 6;40(9):1596-601. PubMed PMID: 12427411.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Beneficial neurohormonal profile of spironolactone in severe congestive heart failure: results from the RALES neurohormonal substudy. AU - Rousseau,Michel F, AU - Gurné,Olivier, AU - Duprez,Daniel, AU - Van Mieghem,Walter, AU - Robert,Annie, AU - Ahn,Sylvie, AU - Galanti,Laurence, AU - Ketelslegers,Jean Marie, AU - ,, PY - 2002/11/13/pubmed PY - 2003/1/7/medline PY - 2002/11/13/entrez SP - 1596 EP - 601 JF - Journal of the American College of Cardiology JO - J. Am. Coll. Cardiol. VL - 40 IS - 9 N2 - OBJECTIVES: 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. SN - 0735-1097 UR - https://www.unboundmedicine.com/medline/citation/12427411/Beneficial_neurohormonal_profile_of_spironolactone_in_severe_congestive_heart_failure:_results_from_the_RALES_neurohormonal_substudy_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0735109702023823 DB - PRIME DP - Unbound Medicine ER -