Detalle Publicación

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

Autores: Cleland, J. G. F. (Autor de correspondencia); 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 Miqueo, Aránzazu; Díez Martínez, Domingo Francisco Javier; Hazebroek, M.; Heymans, S.; Latini, R.; Grojean, S.; Pizard, A.; Girerd, N.; Rossignol, P.; Collier, T. J.; Zannad, F.; HOMAGE Trial Committees and Investigators
Título de la revista: EUROPEAN HEART JOURNAL
ISSN: 0195-668X
Volumen: 42
Número: 6
Páginas: 684 - +
Fecha de publicación: 2021
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 (50mg/day) or control for up to 9 months in people with, or at high risk of, coronary disease and raised plasma &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-1 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 mu g/L; P=0.32] but those receiving spironolactone had greater reductions in PICP (mdiff: -8.1; 95% CI -11.9 to -4.3 mu g/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/m(2); 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.