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 ORCID: https://orcid.org/0000-0001-9241-8890, 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 (2020) 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. (In Press)

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Abstract

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
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
Depositing User: Symplectic
Date Deposited: 16 Sep 2020 15:29
Last Modified: 16 Sep 2020 15:29
URI: https://eprints.keele.ac.uk/id/eprint/8637

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