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

Eur J Heart Fail. 2023 Dec 1. doi: 10.1002/ejhf.3101. Online ahead of print.


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.

PMID:38037709 | DOI:10.1002/ejhf.3101

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