Detalle Publicación

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

Autores: Ferreira JP (Autor de correspondencia); Cleland JGF; Girerd N; Rossignol P; Pellicori P; Cosmi F; Mariottoni B; González Miqueo, Aránzazu; Díez Martínez, Domingo Francisco Javier; Solomon SD; Claggett B; Pfeffer MA; Pitt B; Petutschnigg J; Pieske B; Edelmann F; Zannad F
ISSN: 0167-5273
Volumen: 377
Páginas: 86-88
Fecha de publicación: 2023
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 spi-ronolactone 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.