TY - JOUR
T1 - 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
AU - Cleland, J.G.F.
AU - Ferreira, J.P.
AU - Mariottoni, B.
AU - Pellicori, P.
AU - Cuthbert, J.
AU - Verdonschot, J.A.J.
AU - Petutschnigg, J.
AU - Ahmed, F.Z.
AU - Cosmi, F.
AU - Brunner-La Rocca, H.P.
AU - Mamas, M.A.
AU - Clark, A.L.
AU - Edelmann, F.
AU - Pieske, B.
AU - Khan, J.
AU - McDonald, K.
AU - Rouet, P.
AU - Staessen, J.A.
AU - Mujaj, B.
AU - Gonzalez, A.
AU - Diez, J.
AU - Hazebroek, M.
AU - Heymans, S.
AU - Latini, R.
AU - Grojean, S.
AU - Pizard, A.
AU - Girerd, N.
AU - Rossignol, P.
AU - Collier, T.J.
AU - Zannad, F.
AU - HOMAGE Trial Committees and Investigators
PY - 2021/2/7
Y1 - 2021/2/7
N2 - 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.
AB - 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.
KW - Spironolactone
KW - Heart failure prevention
KW - Fibrosis
KW - Collagen markers
U2 - 10.1093/eurheartj/ehaa758
DO - 10.1093/eurheartj/ehaa758
M3 - Article
C2 - 33215209
SN - 0195-668X
VL - 42
SP - 684
EP - 696
JO - European Heart Journal
JF - European Heart Journal
IS - 6
ER -