Cleland, JGF, Ferreira, JP, Mariottoni, B, Pellicori, P, Cuthbert, J, Verdonschot, JAJ, Petutschnigg, J, Ahmed, F, Cosmi, F, Brunner La Rocca, H-P, Mamas, MA, Clark, AL, Edelmann, F, Pieske, B, Khan, J, McDonald, K, Rouet, P, Stassen, J, Mujaj, B, González, A, Diez, J, Hazebroek, M, Heymanns, S, Latini, R, Grojean, S, Pizard, A, Girerd, N, Rossignol, P, Collier, TJ, Zannad, F and Committees & Investigators, HOMAGE Trial (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) Randomised Clinical Trial. European Heart Journal, 42 (6). pp. 684-696. ISSN 0195-668X

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Importance: Cardiovascular accumulation of collagen (fibrosis) may contribute to the progression from ventricular dysfunction to heart failure. Galectin-3, a potential marker of pro-fibrotic activity, might identify those at greater risk.
Objective: To investigate the effects of spironolactone, according to serum galectin-3 concentration, on serum markers of fibrosis and on cardiac structure and function, in people at increased risk of developing heart failure.
Design: Prospective, randomized, open-label, blinded endpoint (PROBE) trial.
Setting: Clinical research facilities in ten European hospitals.
Participants: People with, or at high-risk of, coronary disease with increased plasma concentrations of B-type natriuretic peptides (BNP or NT-proBNP).
Interventions: spironolactone (up to 50 mg/day) or control for up to nine months.
Main Outcomes and Measures: The primary outcome was the interaction between baseline serum galectin-3 and change in serum procollagen type-III N-terminal pro-peptide (PIIINP), a by-product of type-III collagen synthesis. Serum procollagen type-I C-terminal pro-peptide (PICP) and collagen type-1 C-terminal telopeptide (CITP), respectively reflecting synthesis and degradation of type-I collagen, were also measured.
Results: Of 527 participants, the median age was 73 years and 26% were women. Median follow-up was 267 days. Changes in PIIINP were similar for those assigned to spironolactone and control (mean difference -0.15; 95% confidence interval [CI] -0.44 to 0.15 μg/L; p=0.32) and did not differ when serum galectin-3 was above or below median. Those assigned to spironolactone had greater declines in PICP (mean difference -8.1; -95% CI -11.9 to -4.3 μg/L; p<0.0001) and PICP/CITP ratio (mean difference -2.9; 95% CI -4.3 to -1.5; <0.0001). Systolic blood pressure (mean difference -10; 95% CI -13 to -7 mmHg; p<0.0001), left atrial volume (mean difference -1; 95% CI -2 to 0 mL/m2; p=0.010) and NT-proBNP (mean difference -57; 95% CI -81 to -33 ng/L; p<0.0001) were lower on spironolactone at the final assessment.
Conclusions and Relevance: Spironolactone reduced PICP/CITP ratio, consistent with reduced synthesis and increased degradation of type-I collagen, and reduced NT-proBNP and left atrial volume, suggesting favourable effects on cardiac function. Further research is required to determine whether spironolactone can delay or prevent progression to symptomatic heart failure.

Item Type: Article
Additional Information: © The Author(s) 2020. Published by Oxford University Press on behalf of the European Society of Cardiology. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (, which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact
Uncontrolled Keywords: Spironolactone, Heart failure prevention, Fibrosis, Collagen markers
Subjects: Q Science > Q Science (General)
R Medicine > R Medicine (General)
R Medicine > R Medicine (General) > R735 Medical education. Medical schools. Research
R Medicine > RA Public aspects of medicine
R Medicine > RC Internal medicine > RC666 Diseases of the circulatory (Cardiovascular) system
Divisions: Faculty of Medicine and Health Sciences > School of Primary, Community and Social Care
Depositing User: Symplectic
Date Deposited: 16 Sep 2020 15:29
Last Modified: 12 Mar 2021 11:37

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