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. CONCLUSIONS: 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.
- 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.
- Diez, J.
- Hazebroek, M.
- Heymans, S.
- Latini, R.
- Grojean, S.
- Pizard, A.
- Girerd, N.
- Rossignol, P.
- Collier, T. J.
- Zannad, F.
Keywords
- Aged
- Aging
- Biomarkers
- Female
- Fibrosis
- *Heart Failure/drug therapy
- Humans
- Male
- Peptide Fragments
- Procollagen
- *Spironolactone/therapeutic use
- *Collagen markers
- *Fibrosis
- *Heart failure prevention
- *Spironolactone