title: Effect of eplerenone versus spironolactone on cortisol and hemoglobin A₁(c) levels in patients with chronic heart failure.
abstract: BACKGROUND
  It has been reported that mineralocorticoid receptor antagonist improves the prognosis of chronic heart failure (CHF). Recently, hemoglobin A₁(c) (HbA₁(c)) levels have been reported to be an independent risk factor for mortality in CHF, suggesting the important role of insulin resistance in CHF. We compared the metabolic effect of a selective mineralocorticoid receptor blocker eplerenone with spironolactone in CHF patients.
  
  
  METHODS
  One hundred seven stable outpatients with mild CHF, who were already receiving standard therapy for CHF, were randomized (1:2) to spironolactone (25 mg/d) or eplerenone (50 mg/d). Plasma levels of B-type natriuretic peptide, adiponectin, HbA₁(c) and cortisol were measured before and after 4 months treatment with spironolactone or eplerenone.
  
  
  RESULTS
  There were no differences in baseline characteristics including hemodynamic parameters and plasma levels of biomarkers between 2 groups. In both groups, plasma B-type natriuretic peptide levels were significantly decreased and plasma aldosterone levels were significantly increased after 4 months. In patients receiving spironolactone (n = 34), plasma adiponectin levels were significantly decreased (12.6 ± 1.4-11.2 ± 1.3 μg/mL, P < .0001) and HbA₁(c) and cortisol levels were significantly increased (5.61 ± 0.1-5.8 ± 0.1%, P < .0001, 11.3 ± 0.8-14.7 ± 1.3 μg/dL, P = .003, respectively). In patients receiving spironolactone, there was a significant positive correlation between the change in cortisol and the change in HbA₁(c) (r = 0.489, P = .003). In contrast, in patients receiving eplerenone (n = 73), plasma levels of adiponectin, HbA₁(c) and cortisol did not change.
  
  
  CONCLUSIONS
  These findings indicated that the metabolic effect of eplerenone differed from that of spironolactone and that eplerenone had a superior metabolic effect especially on HbA₁(c) in CHF patients.
authors.affiliation: Cardiovascular and Respiratory Medicine, Shiga University of Medical Science, Tsukinowa, Seta, Otsu, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Yamaji
authors.forename: Takayoshi
authors.initials: T
authors.lastname: Tsutamoto
authors.forename: Chiho
authors.initials: C
authors.lastname: Kawahara
authors.forename: Keizo
authors.initials: K
authors.lastname: Nishiyama
authors.forename: Takashi
authors.initials: T
authors.lastname: Yamamoto
authors.forename: Masanori
authors.initials: M
authors.lastname: Fujii
authors.forename: Minoru
authors.initials: M
authors.lastname: Horie
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D004305:Dose-Response Relationship, Drug; D000077545:Eplerenone; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism*; D006333:Heart Failure / Q000097:blood / Q000188:drug therapy*; D006801:Humans; D006854:Hydrocortisone / Q000097:blood*; D008297:Male; D008875:Middle Aged; D000451:Mineralocorticoid Receptor Antagonists / Q000008:administration & dosage / Q000627:therapeutic use; D013148:Spironolactone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D000077545:Eplerenone; D006442:Glycated Hemoglobin; D006854:Hydrocortisone; D000451:Mineralocorticoid Receptor Antagonists; D013148:Spironolactone