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.

Cleland, John GF; Ferreira, João Pedro; Mariottoni, Beatrice; Pellicori, Pierpaolo; Cuthbert, Joe; Verdonschot, Job AJ; Petutschnigg, Johannes; Ahmed, Fozia Z; Cosmi, Franco; Brunner La Rocca, Hans-Peter; +21 more...Mamas, Mamas A; Clark, Andrew L; Edelmann, Frank; Pieske, Burkert; Khan, Javed; McDonald, Ken; Rouet, Philippe; Staessen, Jan A; Mujaj, Blerim; González, Arantxa; Diez, Javier; Hazebroek, Mark; Heymans, Stephane; Latini, Roberto; Grojean, Stéphanie; Pizard, Anne; Girerd, Nicolas; Rossignol, Patrick; Collier, Tim JORCID logo; Zannad, Faiez; and HOMAGE Trial Committees and Investigators (2021) 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. EUROPEAN HEART JOURNAL, 42 (6). pp. 684-696. ISSN 0195-668X DOI: 10.1093/eurheartj/ehaa758
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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.


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