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, John G F; Mariottoni, Beatrice; Pellicori, Pierpaolo; Cuthbert, Joe; Verdonschot, Job A J; Petutschnigg, Johannes; Ahmed, Fozia Z; Cosmi, Franco; Brunner La Rocca, Hans Peter; Mamas, Mamas A; Clark, Andrew L.; Edelmann, Frank; Pieske, Burkert; Khan, Javed; McDonald, Ken; Rouet, Philippe; Staessen, Jan A; Mujaj, Blerim; González, Arantxa; Diez, Javier; Hazebroek, Mark; Heymans, Stephane; Latini, Roberto; Grojean, Stéphanie; Pizard, Anne; Girerd, Nicolas; Rossignol, Patrick; Collier, Tim J; Zannad, Faiez; the HOMAGE Trial Committees and Investigators

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. Conclusion: 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.

Citation

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., …the HOMAGE Trial Committees and Investigators. (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), 684-696. https://doi.org/10.1093/eurheartj/ehaa758

• Journal Article Type: Article
• Acceptance Date: Sep 5, 2020
• Online Publication Date: Nov 20, 2020
• Publication Date: Feb 7, 2021
• Deposit Date: Jun 8, 2022
• Publicly Available Date: Oct 24, 2024
• Journal: European Heart Journal
• Print ISSN: 0195-668X
• Publisher: Oxford University Press
• Peer Reviewed: Peer Reviewed
• Volume: 42
• Issue: 6
• Pages: 684-696
• DOI: https://doi.org/10.1093/eurheartj/ehaa758
• Keywords: Spironolactone; Heart failure prevention; Fibrosis; Collagen markers
• Public URL: https://hull-repository.worktribe.com/output/3666967