Pierpaolo Pellicori1, João Pedro Ferreira2, Beatrice Mariottoni3, Hans-Peter Brunner-La Rocca4, Fozia Z Ahmed5, Job Verdonschot4, Tim Collier6, Joe J Cuthbert7, Johannes Petutschnigg8,9, Blerim Mujaj10, Nicolas Girerd2, Arantxa González11,12, Andrew L Clark7, Franco Cosmi3, Jan A Staessen10, Stephane Heymans4,13,14, Roberto Latini15, Patrick Rossignol2, Faiez Zannad2, John G F Cleland1. 1. Robertson Institute of Biostatistics and Clinical Trials Unit, University of Glasgow, Glasgow, UK. 2. Université de Lorraine, INSERM, Centre d'Investigations Cliniques Plurithématique, INSERM 1433, CHRU de Nancy,Institut Lorrain du Coeur et des Vaisseaux, FCRIN INI-CRCT, Nancy, France. 3. Department of Cardiology, Cortona Hospital, Arezzo, Italy. 4. Department of Cardiology, Maastricht University Medical Center, Maastricht, The Netherlands. 5. Manchester Heart Centre, Manchester University NHS Foundation Trust, Manchester Academic Health Sciences Centre, Manchester, UK. 6. Department of Medical Statistics, London School of Hygiene and Tropical Medicine, London, UK. 7. Department of Academic Cardiology, Castle Hill Hospital, Hull York Medical School (at University of Hull), Kingston upon Hull, UK. 8. Department of Cardiology, Charité Universitätsmedizin Berlin, Berlin, Germany. 9. DZHK (German Center of Cardiovascular Research), Partner Site Berlin, Berlin, Germany. 10. Studies Coordinating Centre, Research Unit Hypertension and Cardiovascular Epidemiology, KU Leuven Department of Cardiovascular Sciences, University of Leuven, Leuven, Belgium. 11. Program of Cardiovascular Diseases, CIMA Universidad de Navarra and IdiSNA, Pamplona, Spain. 12. CIBERCV, Carlos III Institute of Health, Madrid, Spain. 13. Department of Cardiovascular Sciences, Centre for Molecular and Vascular Biology, KU Leuven, Leuven, Belgium. 14. The Netherlands Heart Institute, Utrecht, The Netherlands. 15. Department of Cardiovascular Medicine, Istituto di Ricerche Farmacologiche Mario Negri, IRCCS, Milan, Italy.
Abstract
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 was73 (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/m2 , 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.
RCT Entities:
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/m2 , 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.
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