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 |
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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 > School of Health & 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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