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 de Lorraine
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

1 University of Glasgow
2 Robertson Centre for Biostatistics, University of Glasgow
3 Institute of Health and Wellbeing
4 DCAC - Défaillance Cardiovasculaire Aiguë et Chronique
5 CIC-P - Centre d'investigation clinique plurithématique Pierre Drouin [Nancy]
6 Cardiovascular & Renal Clinical Trialists - CRCT - French-Clinical Research Infrastructure Network - F-CRIN [Paris]
7 INI-CRCT - Cardiovascular and Renal Clinical Trialists [Vandoeuvre-les-Nancy]
8 Cortona Hospital
9 Castle Hill Hospital
10 University of Hull [United Kingdom]
11 MUMC - Maastricht University Medical Centre
12 Charité - UniversitätsMedizin = Berlin University Medicine
13 BIH - Berlin Institute of Health
14 DZHK - German Center for Cardiovascular Research
15 MAHSC - Manchester Academic Health Science Centre
16 University of Manchester [Manchester]
17 Keele University [Keele]
18 UCD - University College Dublin [Dublin]
19 I2MC - Institut des Maladies Métaboliques et Cardiovasculaires
20 KU Leuven - Catholic University of Leuven = Katholieke Universiteit Leuven
21 Uniklinik - Universitäts Klinikum Freiburg = University Medical Center Freiburg
22 UNAV - Universidad de Navarra [Pamplona]
23 Institute of Health Carlos III
24 IdiSNA - Instituto de Investigación Sanitaria de Navarra [Pamplona, Spain]
25 IRCCS - Istituto di Ricerche Farmacologiche "Mario Negri" = Mario Negri Institute for Pharmacological Research
26 Fondation Force, Research and Consulting Department, EDDH, Centre de Médecine Préventive
27 LSHTM - London School of Hygiene and Tropical Medicine
Job Verdonschot
Franco Cosmi
  • Function : Author
Mark Hazebroek
Dan Atar
  • Function : Author
Lars Kober
  • Function : Author
Kenneth Dickstein
  • Function : Author
Theis Lange
  • Function : Author

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.
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hal-03234930 , version 1 (25-05-2021)

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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-03234930⟩
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