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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

John Cleland 1, 2, 3 João Pedro Ferreira 4, 5, 6, 7 Beatrice Mariottoni 8 Pierpaolo Pellicori 1, 2, 3 Joe Cuthbert 9, 10 Job Verdonschot 11 Johannes Petutschnigg 12, 13, 14 Fozia Ahmed 15 Franco Cosmi 8 Hans-Peter Brunner La Rocca 11 Mamas Mamas 16, 15, 17 Andrew Clark 9, 10 Frank Edelmann 12, 13, 14 Burkert Pieske 12, 13, 14 Javed Khan 1, 2, 3 Ken Mcdonald 18 Philippe Rouet 19 Jan Staessen 20 Blerim Mujaj 20, 21 Arantxa González 22, 23, 24 Javier Diez 22, 23, 24 Mark Hazebroek 11 Stephane Heymans 11 Roberto Latini 25 Stéphanie Grojean 26 Anne Pizard 4, 5, 6, 7 Nicolas Girerd 4, 5, 6, 7 Patrick Rossignol 4, 5, 6, 7 Tim Collier 27 Faiez Zannad 4, 5, 6, 7 Dan Atar Lars Kober Kenneth Dickstein Theis Lange
Abstract : 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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https://hal.univ-lorraine.fr/hal-03234930
Contributor : Erwan Bozec <>
Submitted on : Tuesday, May 25, 2021 - 4:11:47 PM
Last modification on : Friday, May 28, 2021 - 3:11:01 AM

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John Cleland, João Pedro Ferreira, Beatrice Mariottoni, Pierpaolo Pellicori, Joe Cuthbert, et al.. 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, Oxford University Press (OUP): Policy B, 2021, 42 (6), pp.684-696. ⟨10.1093/eurheartj/ehaa758⟩. ⟨hal-03234930⟩

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