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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, ISSN: 1522-9645, Vol: 42, Issue: 6, Page: 684-696
2021
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Article Description

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. 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.

Bibliographic Details

John G F Cleland; João Pedro Ferreira; Beatrice Mariottoni; Pierpaolo Pellicori; Joe Cuthbert; Job A J Verdonschot; Johannes Petutschnigg; Fozia Z Ahmed; Franco Cosmi; Hans-Peter Brunner La Rocca; Mamas A Mamas; Andrew L Clark; Frank Edelmann; Burkert Pieske; Javed Khan; Ken McDonald; Philippe Rouet; Jan A Staessen; Blerim Mujaj; Arantxa González; Javier Diez; Mark Hazebroek; Stephane Heymans; Roberto Latini; Stéphanie Grojean; Anne Pizard; Nicolas Girerd; Patrick Rossignol; Tim J Collier; Faiez Zannad; Dan Atar; Lars Kober; Kenneth Dickstein; Theis Lange

Oxford University Press (OUP)

Medicine

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