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 - Université Paris-Est-Créteil-Val-de-Marne Access content directly
Journal Articles European Heart Journal Year : 2021

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

John Cleland
João Pedro Ferreira
  • Function : Author
Beatrice Mariottoni
  • Function : Author
Pierpaolo Pellicori
Joe Cuthbert
Job Verdonschot
  • Function : Author
Johannes Petutschnigg
Fozia Ahmed
Franco Cosmi
  • Function : Author
Hans-Peter Brunner La Rocca
Mamas Mamas
  • Function : Author
Andrew Clark
  • Function : Author
Frank Edelmann
  • Function : Author
Burkert Pieske
  • Function : Author
Javed Khan
Ken Mcdonald
  • Function : Author
Philippe Rouet
  • Function : Author
Jan Staessen
  • Function : Author
Blerim Mujaj
Arantxa González
  • Function : Author
Javier Diez
  • Function : Author
Mark Hazebroek
Stephane Heymans
  • Function : Author
Roberto Latini
  • Function : Author
Stéphanie Grojean
Nicolas Girerd
  • Function : Author
Patrick Rossignol
  • Function : Author
Tim Collier
Faiez Zannad
Dan Atar
  • Function : Author
Lars Kober
  • Function : Author
Kenneth Dickstein
  • Function : Author
Theis Lange
  • Function : Author

Abstract

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 (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.

Dates and versions

hal-04391514 , version 1 (12-01-2024)

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John Cleland, João Pedro Ferreira, Beatrice Mariottoni, Pierpaolo Pellicori, Joe Cuthbert, et al.. 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. European Heart Journal, 2021, 42 (6), pp.684-696. ⟨10.1093/eurheartj/ehaa758⟩. ⟨hal-04391514⟩

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