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Influence of baseline and worsening renal function on efficacy of spironolactone in patients With severe heart failure: insights from RALES (Randomized Aldactone Evaluation Study).

AbstractOBJECTIVES:
This study investigated the influence of baseline and worsening renal function (WRF) on the efficacy of spironolactone in patients with severe heart failure (HF).
BACKGROUND:
Renal dysfunction or decline in renal function is a known predictor of adverse outcome in patients with HF, and treatment decisions are often on the basis of measures of renal function.
METHODS:
We used data from the RALES (Randomized Aldactone Evaluation Study) in 1,658 patients with New York Heart Association functional class III or IV HF and an ejection fraction <35%. Participants were randomized to spironolactone 25 mg, which could be titrated to 50 mg, or placebo daily. Renal function (estimated glomerular filtration rate [eGFR]) was estimated by the Modification of Diet in Renal Disease equation. Worsening renal function was defined as a 30% reduction in eGFR from baseline to 12 weeks post-randomization.
RESULTS:
Individuals with reduced baseline eGFR exhibited similar relative risk reductions in all-cause death and the combined endpoint of death or hospital stays for HF as those with a baseline eGFR >60 ml/min/1.73 m(2) and greater absolute risk reduction compared with those with a higher baseline eGFR (10.3% vs. 6.4%). Moreover, WRF (17% vs. 7% for spironolactone and placebo groups, p < 0.001) was associated with an increased adjusted risk of death in the placebo group (hazard ratio: 1.9, 95% confidence interval: 1.3 to 2.6) but not in those randomized to spironolactone (hazard ratio: 1.1, 95% confidence interval: 0.79 to 1.5, p interaction = 0.009). The risk of hyperkalemia and renal failure was higher in those with worse baseline renal function and those with WRF, particularly in the spironolactone arm, but the substantial net benefit of spironolactone therapy remained.
CONCLUSIONS:
The absolute benefit of spironolactone was greatest in patients with reduced eGFR. Worsening renal function was associated with a negative prognosis, yet the mortality benefit of spironolactone was maintained.
AuthorsOrly Vardeny, Dong Hong Wu, Akshay Desai, Patrick Rossignol, Faiez Zannad, Bertram Pitt, Scott D Solomon, RALES Investigators
JournalJournal of the American College of Cardiology (J Am Coll Cardiol) Vol. 60 Issue 20 Pg. 2082-9 (Nov 13 2012) ISSN: 1558-3597 [Electronic] United States
PMID23083787 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2012 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
Chemical References
  • Diuretics
  • Spironolactone
Topics
  • Diuretics (pharmacology, therapeutic use)
  • Double-Blind Method
  • Female
  • Glomerular Filtration Rate (drug effects)
  • Heart Failure (drug therapy, mortality, physiopathology)
  • Hospitalization
  • Humans
  • Length of Stay
  • Male
  • Prognosis
  • Risk Factors
  • Spironolactone (pharmacology, therapeutic use)
  • Treatment Outcome

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