TY - JOUR
T1 - Effects of spironolactone on serum markers of fibrosis in people at high risk of developing heart failure
T2 - rationale, design and baseline characteristics of a proof-of-concept, randomised, precision-medicine, prevention trial. The Heart OMics in AGing (HOMAGE) trial
AU - Pellicori, Pierpaolo
AU - Ferreira, Joao Pedro
AU - Mariottoni, Beatrice
AU - Brunner-La Rocca, Hans-Peter
AU - Ahmed, Fozia Z.
AU - Verdonschot, Job
AU - Collier, Tim
AU - Cuthbert, Joe J.
AU - Petutschnigg, Johannes
AU - Mujaj, Blerim
AU - Girerd, Nicolas
AU - Gonzalez, Arantxa
AU - Clark, Andrew L.
AU - Cosmi, Franco
AU - Staessen, Jan A.
AU - Heymans, Stephane
AU - Latini, Roberto
AU - Rossignol, Patrick
AU - Zannad, Faiez
AU - Cleland, John G. F.
N1 - Funding Information:
Authors are immensely grateful to Sylvia Van Haren, Heiko Breek and Stéphanie Grosjean for their valuable support throughout the duration of this trial. The research leading to these results has received funding from the European Union Commission's Seventh Framework programme under grant agreement no. 305507 (Homage). We acknowledge the support to SH from the Netherlands Cardiovascular Research Initiative, an initiative with support of the Dutch Heart Foundation, CVON2016‐Early HFPEF, 2015‐10, CVON She‐PREDICTS, grant 2017‐21. We acknowledge the support to SH of the ERA‐Net‐CVD project MacroERA, 01KL1706. JF, NG, P.R. and F.Z. are supported by a public grant overseen by the French National Research Agency (ANR) as part of the second ‘Investissements d'Avenir’ program FIGHT‐HF (reference: ANR‐15‐RHU‐0004) and by the French PIA project ‘Lorraine Université d'Excellence’, reference ANR‐15‐IDEX‐04‐LUE, and by the Contrat de plan Etat‐lorraine and FEDER lorraine. This work was supported, in part, by the British Heart Foundation Centre of Research Excellence grant number RE/18/6/34217.
Funding Information:
Authors are immensely grateful to Sylvia Van Haren, Heiko Breek and St?phanie Grosjean for their valuable support throughout the duration of this trial. The research leading to these results has received funding from the European Union Commission's Seventh Framework programme under grant agreement no. 305507 (Homage). We acknowledge the support to SH from the Netherlands Cardiovascular Research Initiative, an initiative with support of the Dutch Heart Foundation, CVON2016-Early HFPEF, 2015-10, CVON She-PREDICTS, grant 2017-21. We acknowledge the support to SH of the ERA-Net-CVD project MacroERA, 01KL1706. JF, NG, P.R. and F.Z. are supported by a public grant overseen by the French National Research Agency (ANR) as part of the second ?Investissements d'Avenir? program FIGHT-HF (reference: ANR-15-RHU-0004) and by the French PIA project ?Lorraine Universit? d'Excellence?, reference ANR-15-IDEX-04-LUE, and by the Contrat de plan Etat-lorraine and FEDER lorraine. This work was supported, in part, by the British Heart Foundation Centre of Research Excellence grant number RE/18/6/34217. Conflict of interest: P.R. reports personal fees (consulting) for Idorsia and G3P, honoraria from AstraZeneca, Bayer, CVRx, Fresenius, Grunenthal, Novartis, NovoNordisk, Servier, Stealth Peptides, Ablative Solutions, Corvidia, Relypsa and Vifor Fresenius Medical Care Renal Pharma, outside the submitted work. P.R. is the cofounder of CardioRenal. The other authors report no conflicts of interest.
Publisher Copyright:
© 2020 European Society of Cardiology
PY - 2020/9
Y1 - 2020/9
N2 - AimsAsymptomatic patients with coronary artery disease (CAD), hypertension and/or type 2 diabetes mellitus (T2DM) are at greater risk of developing heart failure (HF). Fibrosis, leading to myocardial and vascular dysfunction, might be an important pathway of progression. The Heart OMics in AGing (HOMAGE) trial aims to investigate the effects of spironolactone on serum markers of collagen metabolism and on cardiovascular structure and function in people at risk of developing HF and potential interactions with a marker of fibrogenic activity, galectin-3.Methods and resultsThe HOMAGE trial is a prospective, randomised, open-label, blinded endpoint (PROBE) study comparing spironolactone (up to 50mg/day) and standard care over 9months in people with clinical risk factors for developing HF, including hypertension, CAD and T2DM, and elevated plasma concentrations of N-terminal pro-B-type natriuretic peptide (NT-proBNP, 125 to 1000ng/L) or B-type natriuretic peptide (BNP, 35 to 280ng/L). Exclusion criteria included left ventricular ejection fractionConclusionsThe HOMAGE trial will provide insights on the effect of spironolactone on pathways that might drive progression to HF. Clinical Trial Registration: ClinicalTrials.gov NCT02556450.
AB - AimsAsymptomatic patients with coronary artery disease (CAD), hypertension and/or type 2 diabetes mellitus (T2DM) are at greater risk of developing heart failure (HF). Fibrosis, leading to myocardial and vascular dysfunction, might be an important pathway of progression. The Heart OMics in AGing (HOMAGE) trial aims to investigate the effects of spironolactone on serum markers of collagen metabolism and on cardiovascular structure and function in people at risk of developing HF and potential interactions with a marker of fibrogenic activity, galectin-3.Methods and resultsThe HOMAGE trial is a prospective, randomised, open-label, blinded endpoint (PROBE) study comparing spironolactone (up to 50mg/day) and standard care over 9months in people with clinical risk factors for developing HF, including hypertension, CAD and T2DM, and elevated plasma concentrations of N-terminal pro-B-type natriuretic peptide (NT-proBNP, 125 to 1000ng/L) or B-type natriuretic peptide (BNP, 35 to 280ng/L). Exclusion criteria included left ventricular ejection fractionConclusionsThe HOMAGE trial will provide insights on the effect of spironolactone on pathways that might drive progression to HF. Clinical Trial Registration: ClinicalTrials.gov NCT02556450.
KW - HOMAGE
KW - Spironolactone
KW - Fibrosis
KW - Biomarkers
KW - Study design
KW - PRESERVED EJECTION FRACTION
KW - EXTRACELLULAR-MATRIX TURNOVER
KW - BRAIN NATRIURETIC PEPTIDE
KW - DOUBLE-BLIND
KW - ALDOSTERONE ANTAGONISM
KW - DIASTOLIC DYSFUNCTION
KW - MYOCARDIAL-INFARCTION
KW - COLLAGEN TURNOVER
KW - NT-PROBNP
KW - BIOMARKERS
U2 - 10.1002/ejhf.1716
DO - 10.1002/ejhf.1716
M3 - Article
C2 - 31950604
SN - 1388-9842
VL - 22
SP - 1711
EP - 1723
JO - European journal of heart failure
JF - European journal of heart failure
IS - 9
ER -