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

Cleland, J. G.F. et al. (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. European Heart Journal, 42(6), pp. 684-696. (doi: 10.1093/eurheartj/ehaa758) (PMID:33215209) (PMCID:PMC7878013)

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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.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Cleland, Professor John and Pellicori, Dr Pierpaolo
Authors: 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., and Zannad, F.
College/School:College of Medical Veterinary and Life Sciences > Institute of Health and Wellbeing > Robertson Centre
Journal Name:European Heart Journal
Publisher:Oxford University Press
ISSN:0195-668X
ISSN (Online):1522-9645
Published Online:20 November 2020
Copyright Holders:Copyright © 2020 The Authors
First Published:First published in European Heart Journal 42(6): 684-696
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
190666HOMAGE: Heart OMics in AGEingChristian DellesEuropean Commission (EC)305507Institute of Cardiovascular & Medical Sciences