Effects of empagliflozin on collagen biomarkers in patients with heart failure: Findings from the EMPEROR trials

Autores da FMUP
Participantes de fora da FMUP
- Butler, J
- Anker, SD
- Januzzi, JL
- Panova-Noeva, M
- Reese-Petersen, AL
- Sattar, N
- Schueler, E
- Pocock, SJ
- Filippatos, G
- Packer, M
- Sumin, M
- Zannad, F
- EMPEROR Comm & Investigators
Unidades de investigação
Abstract
Aims Extracellular matrix remodelling is one of the key pathways involved in heart failure (HF) progression. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) may have a role in attenuating myocardial fibrosis. The impact of SGLT2i on blood markers of collagen turnover in humans is not fully elucidated. This study aimed to investigate the effect of empagliflozin on serum markers of collagen turnover in patients enrolled in the EMPEROR-Preserved and EMPEROR-Reduced trials.Methods and results Overall, 1084 patients (545 in empagliflozin and 539 in placebo) were included in the analysis. Procollagen type I carboxy-terminal propeptide (PICP), a fragment of N-terminal type III collagen (PRO-C3), procollagen type I amino-terminal peptide (PINP), a fragment of C-terminal type VIa3 collagen (PRO-C6), a fragment of type I collagen (C1M), and a fragment of type III collagen (C3M) were measured in serum at baseline, 12 and 52 weeks. A mixed model repeated measurements model was used to evaluate the effect of empagliflozin versus placebo on the analysed biomarkers. 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: geometric mean ratio = 0.95, 95% confidence interval [CI] 0.91-0.99, p = 0.012; week 52: geometric mean ratio = 0.92, 95% CI 0.88-0.97, p = 0.003). Additionally, empagliflozin reduced PRO-C3 at week 52 by 7% (week 12: geometric mean ratio = 0.98, 95% CI 0.95-1.02, p = 0.42; week 52: geometric mean 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 SGLT2i in HF remains to be elucidated.
Dados da publicação
- ISSN/ISSNe:
- 1388-9842, 1879-0844
- Tipo:
- Article
- Páginas:
- 274-284
- DOI:
- 10.1002/ejhf.3101
- Link para outro recurso:
- www.scopus.com
European Journal of Heart Failure Wiley-Blackwell
Citações Recebidas na Web of Science: 1
Citações Recebidas na Scopus: 6
Documentos
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Filiações
Keywords
- Collagen biomarkers; Empagliflozin; Fibrosis; Heart failure
Campos de estudo
Financiamento
Proyectos asociados
Dapagliflozin, Spironolactone or Both for HFpEF (SOGALDI-PEF) - NCT05676684
Investigador Principal: João Pedro Melo Marques Pinho Ferreira
Ensaio Clínico Académico (SOGALDI-PEF) . AstraZeneca . 2022
Initiation of ARNi and SGLT2i in Patients With HFrEF: Randomized Open-label Trial (INITIATE-HFrEF) -NCT05989503
Investigador Principal: João Pedro Melo Marques Pinho Ferreira
Ensaio Clínico Académico (INITIATE-HFrEF) . Novartis . 2023
Citar a publicação
Ferreira JP,Butler J,Anker SD,Januzzi JL,Panova M,Reese AL,Sattar N,Schueler E,Pocock SJ,Filippatos G,Packer M,Sumin M,Zannad F,EMPEROR Comm Investigators &. Effects of empagliflozin on collagen biomarkers in patients with heart failure: Findings from the EMPEROR trials. Eur. J. Heart Fail. 2023. 26. (2):p. 274-284. IF:18,200. (1).