Science and Research

The effect of spironolactone on cardiovascular function and markers of fibrosis in people at increased risk of developing heart failure: the heart 'OMics' in AGEing (HOMAGE) randomized clinical trial

AIMS: To investigate the effects of spironolactone on fibrosis and cardiac function in people at increased risk of developing heart failure. METHODS AND RESULTS: Randomized, open-label, blinded-endpoint trial comparing spironolactone (50 mg/day) or control for up to 9 months in people with, or at high risk of, coronary disease and raised plasma B-type natriuretic peptides. The primary endpoint was the interaction between baseline serum galectin-3 and changes in serum procollagen type-III N-terminal pro-peptide (PIIINP) in participants assigned to spironolactone or control. Procollagen type-I C-terminal pro-peptide (PICP) and collagen type-1 C-terminal telopeptide (CITP), reflecting synthesis and degradation of type-I collagen, were also measured. In 527 participants (median age 73 years, 26% women), changes in PIIINP were similar for spironolactone and control [mean difference (mdiff): -0.15; 95% confidence interval (CI) -0.44 to 0.15 μg/L; P = 0.32] but those receiving spironolactone had greater reductions in PICP (mdiff: -8.1; 95% CI -11.9 to -4.3 μg/L; P < 0.0001) and PICP/CITP ratio (mdiff: -2.9; 95% CI -4.3 to -1.5; <0.0001). No interactions with serum galectin were observed. Systolic blood pressure (mdiff: -10; 95% CI -13 to -7 mmHg; P < 0.0001), left atrial volume (mdiff: -1; 95% CI -2 to 0 mL/m2; P = 0.010), and NT-proBNP (mdiff: -57; 95% CI -81 to -33 ng/L; P < 0.0001) were reduced in those assigned spironolactone. CONCLUSIONS: Galectin-3 did not identify greater reductions in serum concentrations of collagen biomarkers in response to spironolactone. However, spironolactone may influence type-I collagen metabolism. Whether spironolactone can delay or prevent progression to symptomatic heart failure should be investigated.
  • Cleland, J. G. F.
  • Ferreira, J. P.
  • Mariottoni, B.
  • Pellicori, P.
  • Cuthbert, J.
  • Verdonschot, J. A. J.
  • Petutschnigg, J.
  • Ahmed, F. Z.
  • Cosmi, F.
  • Brunner La Rocca, H. P.
  • Mamas, M. A.
  • Clark, A. L.
  • Edelmann, F.
  • Pieske, B.
  • Khan, J.
  • McDonald, K.
  • Rouet, P.
  • Staessen, J. A.
  • Mujaj, B.
  • González, A.
  • Diez, J.
  • Hazebroek, M.
  • Heymans, S.
  • Latini, R.
  • Grojean, S.
  • Pizard, A.
  • Girerd, N.
  • Rossignol, P.
  • Collier, T. J.
  • Zannad, F.

Keywords

  • Aged
  • Aging
  • Biomarkers
  • Female
  • Fibrosis
  • *Heart Failure/drug therapy
  • Humans
  • Male
  • Peptide Fragments
  • Procollagen
  • *Spironolactone/therapeutic use
  • *Collagen markers
  • *Fibrosis
  • *Heart failure prevention
  • *Spironolactone
Publication details
DOI: 10.1093/eurheartj/ehaa758
Journal: Eur Heart J
Pages: 684-696 
Number: 6
Work Type: Original
Location: Assoziierter Partner
Disease Area: CFBE
Partner / Member: BIH
Access-Number: 33215209

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