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

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

Data de publicação: Data Ahead of Print:

Autores da FMUP

  • João Pedro Melo Marques Pinho Ferreira

    Autor

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

European Journal of Heart Failure  Wiley-Blackwell

Tipo:
Article
Páginas:
274-284
Link para outro recurso:
www.scopus.com

Citações Recebidas na Web of Science: 1

Citações Recebidas na Scopus: 6

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Keywords

  • Collagen biomarkers; Empagliflozin; Fibrosis; Heart failure

Campos de estudo

Financiamento

Boehringer Ingelheim

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

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