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

J.G.F. Cleland*, J.P. Ferreira, B. Mariottoni, P. Pellicori, J. Cuthbert, J.A.J. Verdonschot, J. Petutschnigg, F.Z. Ahmed, F. Cosmi, H.P. Brunner-La Rocca, M.A. Mamas, A.L. Clark, F. Edelmann, B. Pieske, J. Khan, K. McDonald, P. Rouet, J.A. Staessen, B. Mujaj, A. GonzalezJ. Diez, M. Hazebroek, S. Heymans, R. Latini, S. Grojean, A. Pizard, N. Girerd, P. Rossignol, T.J. Collier, F. Zannad, HOMAGE Trial Committees and Investigators

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

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 (50mg/day) or control for up to 9 months in people with, or at high risk of, coronary disease and raised plasma &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-1 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 mu g/L; P=0.32] but those receiving spironolactone had greater reductions in PICP (mdiff: -8.1; 95% CI -11.9 to -4.3 mu g/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/m(2); P = 0.010), and NT-proBNP (mdiff: -57; 95% CI -81 to -33 ng/L; P< 0.0001) were reduced in those assigned spironolactone.Conclusion 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.
Original languageEnglish
Pages (from-to)684-696
Number of pages15
JournalEuropean Heart Journal
Volume42
Issue number6
DOIs
Publication statusPublished - 7 Feb 2021

Keywords

  • Spironolactone
  • Heart failure prevention
  • Fibrosis
  • Collagen markers

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