Spironolactone effect on circulating procollagen type I carboxy-terminal propeptide: pooled analysis of three randomized trials

Ferreira, J. P. et al. (2023) Spironolactone effect on circulating procollagen type I carboxy-terminal propeptide: pooled analysis of three randomized trials. International Journal of Cardiology, 377, pp. 86-88. (doi: 10.1016/j.ijcard.2023.01.088) (PMID:36738846)

[img] Text
291589.pdf - Accepted Version
Restricted to Repository staff only until 2 February 2024.
Available under License Creative Commons Attribution Non-commercial No Derivatives.

[img] Text
291589Suppl.pdf - Supplemental Material
Restricted to Repository staff only until 2 February 2024.



Background: Spironolactone might improve the prognosis of patients with heart failure with preserved left ventricular ejection fraction (HFpEF), but the mechanisms by which it acts are uncertain. Serum concentrations of procollagen type I carboxy-terminal propeptide (PICP) reflect the synthesis of type I collagen and correlate well with histologically proven cardiac fibrosis. Aims: To investigate the effect of spironolactone on serum PICP concentration in patients with stage B and C HFpEF across three trials (HOMAGE, ALDO-DHF, and TOPCAT) for which measurements of serum PICP were available. Methods: Random-effects meta-analysis. Results: A total of 1038 patients with PICP measurements available both at baseline and 9–12 months were included in this analysis: 488 (47.0%) from HOMAGE, 386 (37.2%) from ALDO-DHF, and 164 (15.8%) from TOPCAT. The median (percentile25–75) serum PICP was 98 (76–128) ng/mL. Compared to placebo or usual care, administration of spironolactone for 9 to 12 months reduced serum PICP by −7.4 ng/mL, 95%CI -13.9 to −0.9, P-value =0.02. The effect was moderately heterogeneous (I2 = 64%) with the most pronounced effect seen in TOPCAT where PICP was reduced by −27.0 ng/mL, followed by HOMAGE where PICP was reduced by −8.1 ng/mL, and was least marked in ALDO-DHF where PICP changed by −2.9 ng/mL. The association between spironolactone and serum PICP was not mediated substantially by blood pressure. Conclusions: Spironolactone reduced serum concentrations of PICP in patients with HFpEF with different severity and stages of disease. These findings are consistent with spironolactone having an anti-fibrotic effect.

Item Type:Articles
Glasgow Author(s) Enlighten ID:Cleland, Professor John and Ferreira, Mr Joao Pedro and Pellicori, Dr Pierpaolo
Authors: Ferreira, J. P., Cleland, J. G., Girerd, N., Rossignol, P., Pellicori, P., Cosmi, F., Mariottoni, B., González, A., Diez, J., Solomon, S. D., Claggett, B., Pfeffer, M. A., Pitt, B., Petutschnigg, J., Pieske, B., Edelmann, F., and Zannad, F.
College/School:College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
Journal Name:International Journal of Cardiology
ISSN (Online):1874-1754
Published Online:02 February 2023
Copyright Holders:Copyright © 2023 Elsevier B.V.
First Published:First published in International Journal of Cardiology 377: 86-88
Publisher Policy:Reproduced in accordance with the publisher copyright policy

University Staff: Request a correction | Enlighten Editors: Update this record

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