PMID- 31950604 OWN - NLM STAT- MEDLINE DCOM- 20210518 LR - 20210518 IS - 1879-0844 (Electronic) IS - 1388-9842 (Linking) VI - 22 IP - 9 DP - 2020 Sep TI - Effects of spironolactone on serum markers of fibrosis in people at high risk of developing heart failure: rationale, design and baseline characteristics of a proof-of-concept, randomised, precision-medicine, prevention trial. The Heart OMics in AGing (HOMAGE) trial. PG - 1711-1723 LID - 10.1002/ejhf.1716 [doi] AB - AIMS: Asymptomatic 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 RESULTS: The HOMAGE trial is a prospective, randomised, open-label, blinded endpoint (PROBE) study comparing spironolactone (up to 50 mg/day) and standard care over 9 months 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 1000 ng/L) or B-type natriuretic peptide (BNP, 35 to 280 ng/L). Exclusion criteria included left ventricular ejection fraction < 45%, atrial fibrillation, severe renal dysfunction, or treatment with loop diuretics. The primary endpoint was the interaction between change in serum concentrations of procollagen type III N-terminal propeptide (PIIINP) and treatment with spironolactone according to median plasma concentrations of galectin-3 at baseline. For the 527 participants enrolled, median (interquartile range) age was 73 (69-79) years, 135 (26%) were women, 412 (78%) had hypertension, 377 (72%) CAD, and 212 (40%) T2DM. At baseline, medians (interquartile ranges) were for left ventricular ejection fraction 63 (58-67) %, for left atrial volume index 31 (26-37) mL/m(2) , for plasma NT-proBNP 214 (137-356) ng/L, for serum PIIINP 3.9 (3.1-5.0) ng/mL, and for galectin-3 16.1 (13.5-19.7) ng/mL. CONCLUSIONS: The HOMAGE trial will provide insights on the effect of spironolactone on pathways that might drive progression to HF. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT02556450. CI - (c) 2020 European Society of Cardiology. FAU - Pellicori, Pierpaolo AU - Pellicori P AD - Robertson Institute of Biostatistics and Clinical Trials Unit, University of Glasgow, Glasgow, UK. FAU - Ferreira, Joao Pedro AU - Ferreira JP AD - Universite de Lorraine, INSERM, Centre d'Investigations Cliniques Plurithematique, INSERM 1433, CHRU de Nancy,Institut Lorrain du Coeur et des Vaisseaux, FCRIN INI-CRCT, Nancy, France. FAU - Mariottoni, Beatrice AU - Mariottoni B AD - Department of Cardiology, Cortona Hospital, Arezzo, Italy. FAU - Brunner-La Rocca, Hans-Peter AU - Brunner-La Rocca HP AD - Department of Cardiology, Maastricht University Medical Center, Maastricht, The Netherlands. FAU - Ahmed, Fozia Z AU - Ahmed FZ AD - Manchester Heart Centre, Manchester University NHS Foundation Trust, Manchester Academic Health Sciences Centre, Manchester, UK. FAU - Verdonschot, Job AU - Verdonschot J AD - Department of Cardiology, Maastricht University Medical Center, Maastricht, The Netherlands. FAU - Collier, Tim AU - Collier T AD - Department of Medical Statistics, London School of Hygiene and Tropical Medicine, London, UK. FAU - Cuthbert, Joe J AU - Cuthbert JJ AD - Department of Academic Cardiology, Castle Hill Hospital, Hull York Medical School (at University of Hull), Kingston upon Hull, UK. FAU - Petutschnigg, Johannes AU - Petutschnigg J AD - Department of Cardiology, Charite Universitatsmedizin Berlin, Berlin, Germany. AD - DZHK (German Center of Cardiovascular Research), Partner Site Berlin, Berlin, Germany. FAU - Mujaj, Blerim AU - Mujaj B AD - Studies Coordinating Centre, Research Unit Hypertension and Cardiovascular Epidemiology, KU Leuven Department of Cardiovascular Sciences, University of Leuven, Leuven, Belgium. FAU - Girerd, Nicolas AU - Girerd N AD - Universite de Lorraine, INSERM, Centre d'Investigations Cliniques Plurithematique, INSERM 1433, CHRU de Nancy,Institut Lorrain du Coeur et des Vaisseaux, FCRIN INI-CRCT, Nancy, France. FAU - Gonzalez, Arantxa AU - Gonzalez A AD - Program of Cardiovascular Diseases, CIMA Universidad de Navarra and IdiSNA, Pamplona, Spain. AD - CIBERCV, Carlos III Institute of Health, Madrid, Spain. FAU - Clark, Andrew L AU - Clark AL AD - Department of Academic Cardiology, Castle Hill Hospital, Hull York Medical School (at University of Hull), Kingston upon Hull, UK. FAU - Cosmi, Franco AU - Cosmi F AD - Department of Cardiology, Cortona Hospital, Arezzo, Italy. FAU - Staessen, Jan A AU - Staessen JA AD - Studies Coordinating Centre, Research Unit Hypertension and Cardiovascular Epidemiology, KU Leuven Department of Cardiovascular Sciences, University of Leuven, Leuven, Belgium. FAU - Heymans, Stephane AU - Heymans S AD - Department of Cardiology, Maastricht University Medical Center, Maastricht, The Netherlands. AD - Department of Cardiovascular Sciences, Centre for Molecular and Vascular Biology, KU Leuven, Leuven, Belgium. AD - The Netherlands Heart Institute, Utrecht, The Netherlands. FAU - Latini, Roberto AU - Latini R AD - Department of Cardiovascular Medicine, Istituto di Ricerche Farmacologiche Mario Negri, IRCCS, Milan, Italy. FAU - Rossignol, Patrick AU - Rossignol P AD - Universite de Lorraine, INSERM, Centre d'Investigations Cliniques Plurithematique, INSERM 1433, CHRU de Nancy,Institut Lorrain du Coeur et des Vaisseaux, FCRIN INI-CRCT, Nancy, France. FAU - Zannad, Faiez AU - Zannad F AD - Universite de Lorraine, INSERM, Centre d'Investigations Cliniques Plurithematique, INSERM 1433, CHRU de Nancy,Institut Lorrain du Coeur et des Vaisseaux, FCRIN INI-CRCT, Nancy, France. FAU - Cleland, John G F AU - Cleland JGF AD - Robertson Institute of Biostatistics and Clinical Trials Unit, University of Glasgow, Glasgow, UK. LA - eng SI - ClinicalTrials.gov/NCT02556450 GR - ANR-15-IDEX-04-LUE/French PIA/International GR - ANR-15-RHU-0004/French National Research Agency (ANR)/International GR - 01KL1706/ERA-Net-CVD/International GR - 2017-21/CVON She-PREDICTS/International GR - 2015-10/CVON2016-Early HFPEF/International GR - 305507/European Union Commission's Seventh Framework programme/International PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20200116 PL - England TA - Eur J Heart Fail JT - European journal of heart failure JID - 100887595 RN - 0 (Biomarkers) RN - 0 (Peptide Fragments) RN - 114471-18-0 (Natriuretic Peptide, Brain) RN - 27O7W4T232 (Spironolactone) SB - IM MH - Aged MH - Aging MH - Biomarkers MH - Diabetes Mellitus, Type 2 MH - Female MH - Fibrosis MH - *Heart Failure/drug therapy/prevention & control MH - Humans MH - Male MH - Natriuretic Peptide, Brain MH - Peptide Fragments MH - Prospective Studies MH - Spironolactone MH - Stroke Volume MH - Ventricular Function, Left OTO - NOTNLM OT - Biomarkers OT - Fibrosis OT - HOMAGE OT - Spironolactone OT - Study design EDAT- 2020/01/18 06:00 MHDA- 2021/05/19 06:00 CRDT- 2020/01/18 06:00 PHST- 2019/10/31 00:00 [received] PHST- 2019/11/18 00:00 [revised] PHST- 2019/11/21 00:00 [accepted] PHST- 2020/01/18 06:00 [pubmed] PHST- 2021/05/19 06:00 [medline] PHST- 2020/01/18 06:00 [entrez] AID - 10.1002/ejhf.1716 [doi] PST - ppublish SO - Eur J Heart Fail. 2020 Sep;22(9):1711-1723. doi: 10.1002/ejhf.1716. Epub 2020 Jan 16.