cover image: Effects of empaglifozin on collagen biomarkers in patients with Heart Failure. Findings from the EMPEROR trials

Effects of empaglifozin on collagen biomarkers in patients with Heart Failure. Findings from the EMPEROR trials

1 Dec 2023

Abstract Background Extracellular matrix remodeling is one of the key pathways involved in heart failure (HF) progression. SGLT2 inhibitors may have a role in attenuating myocardial fibrosis. The impact of SGLT2 inhibitors on blood markers of collagen turnover in humans is not fully elucidated. Aims To investigate the effect of empagliflozin on serum markers of collagen turnover in patients enrolled in the EMPEROR‐Preserved and EMPEROR‐Reduced trials. Methods 1084 patients (545 in empagliflozin and 539 in placebo) were included in the analysis. PICP, PRO‐C3, PINP, PRO‐C6, C1M, and C3M were measured in serum at baseline, 12 and 52 weeks. A mixed model repeated measurements model (MMRM) was used to evaluate the effect of empagliflozin vs. placebo on the analysed biomarkers. Results Higher baseline PICP, PRO‐C6 and PINP levels were associated with older age, a more severe HF presentation, higher levels of natriuretic peptides and high‐sensitivity troponin T, and the presence of comorbid conditions such as chronic kidney disease and atrial fibrillation. Higher PICP levels were associated with the occurrence of the study primary endpoint (a composite of HF hospitalization or cardiovascular death), and PRO‐C6 and PINP were associated with the occurrence of sustained worsening of kidney function. On the other hand, PRO‐C3, C1M, and C3M were not associated with worse HF severity or study outcomes. Compared to placebo, empagliflozin reduced PICP at week 12 by 5% and at week 52 by 8% (week 12 gMean ratio = 0.95, 95%CI [0.91, 0.99], p = 0.012; week 52 gMean ratio = 0.92, 95%CI [0.88, 0.97], p = 0.003). Additionally, empagliflozin reduced PRO‐C3 at week 52 by 7% (week 12 gMean ratio = 0.98, 95%CI [0.95, 1.02], p = 0.42; week 52 gMean ratio = 0.93, 95%CI [0.89, 0.98], p = 0.003), without impact on other collagen markers. Conclusion Our observations are consistent with experimental observations that empagliflozin down‐regulates profibrotic signalling. The importance of such an effect for the clinical benefits of SGLT2 inhibitors in HF remains to be elucidated. This article is protected by copyright. All rights reserved.

Authors

João Pedro Ferreira, Javed Butler, Stefan Anker, James Januzzi, Marina Panova-Noeva, Alexander Reese-Petersen, Naveed Sattar, Elke Schueler, Stuart Pocock, Gerasimos Filippatos, Milton Packer, Mikhail Sumin, Faiez Zannad

Bibliographic Reference
João Pedro Ferreira, Javed Butler, Stefan Anker, James Januzzi, Marina Panova-Noeva, et al.. Effects of empaglifozin on collagen biomarkers in patients with Heart Failure. Findings from the EMPEROR trials. European Journal of Heart Failure, 2023, ⟨10.1002/ejhf.3101⟩. ⟨hal-04324690⟩
DOI
https://doi.org/10.1002/ejhf.3101
Department
German Centre for Cardiovascular Research (DZHK) partner site Berlin
Funding
The EMPEROR-Reduced and Preserved trials were funded by Boehringer Ingelheim and Eli Lilly
HAL Collection
['Publications du LORIA', 'Université de Lorraine', 'DCAC - Défaillance Cardiovasculaire Aiguë et Chronique', 'Pôle scientifique Biologie, Médecine, Santé']
HAL Identifier
4324690
Institution
['Centre Hospitalier Régional Universitaire de Nancy', 'Institut National de la Santé et de la Recherche Médicale', 'Université de Lorraine', 'Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu [Nancy]', 'French-Clinical Research Infrastructure Network - F-CRIN [Paris]', 'Faculdade de Medicina da Universidade do Porto', 'Cardiovascular Research and Development Center (UnIC@RISE)', 'Baylor Scott & White Research Institute', 'University of Mississippi Medical Center', 'Charité - UniversitätsMedizin = Charité - University Hospital [Berlin]', 'Berlin Institute of Health', 'Wrocław Medical University', 'Massachusetts General Hospital [Boston]', 'Harvard Medical School [Boston]', 'Boehringer Ingelheim Pharma GmbH & Co. KG', 'Nordic Bioscience A', 'S, CCBR', 'mainanalytics GmbH', 'London School of Hygiene and Tropical Medicine', '“Attikon” University Hospital', 'Baylor College of Medecine', 'Imperial College London', 'Boehringer Ingelheim International GmbH']
Laboratory
['Défaillance Cardiovasculaire Aiguë et Chronique', "Centre d'investigation clinique plurithématique Pierre Drouin [Nancy]", 'Cardiovascular and Renal Clinical Trialists [Vandoeuvre-les-Nancy]', 'German Center for Cardiovascular Research', 'Nordic Bioscience A', 'S, CCBR', 'Baylor University Medical Center']
Published in
France

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