The effect of empagliflozin on growth differentiation factor 15 in patients with heart failure: a randomized controlled trial (Empire HF Biomarker)

Cardiovascular Diabetology

Christian Tuxen¹  Jesper Jensen²  Morten Schou²  Lars Videbæk³  Julie H. Larsen³  Jacob Eifer Møller⁴  Massar Omar⁵  Finn Gustafsson⁶  Lars Køber⁶  Camilla F. Andersen⁷  Caroline Kistorp⁸  Kurt Højlund⁹ 

[1] Department of Cardiology, Bispebjerg, Frederiksberg University Hospital, Copenhagen, Denmark;Department of Cardiology, Herlev, Gentofte University Hospital, Herlev, Denmark;Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark;Department of Cardiology, Research Unit of Cardiology, Odense University Hospital, Odense, Denmark;Department of Cardiology, Research Unit of Cardiology, Odense University Hospital, Odense, Denmark;Department of Cardiology, Rigshospitalet, Copenhagen, Denmark;Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark;Department of Cardiology, Research Unit of Cardiology, Odense University Hospital, Odense, Denmark;Steno Diabetes Center Odense, Odense University Hospital, Odense, Denmark;Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark;Department of Cardiology, Rigshospitalet, Copenhagen, Denmark;Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark;Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark;Department of Endocrinology, Rigshospitalet, Copenhagen, Denmark;Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark;Steno Diabetes Center Odense, Odense University Hospital, Odense, Denmark;

关键词: HFrEF;    SGLT2 inhibitors;    GDF15;    hsTNT;    hsCRP;   

DOI  :  10.1186/s12933-022-01463-2

来源: Springer

【 摘 要 】

BackgroundPlasma growth differentiation factor-15 (GDF-15) biomarker levels increase in response to inflammation and tissue injury, and increased levels of GDF-15 are associated with increased risk of mortality in patients with heart failure with reduced ejection fraction (HFrEF). Sodium-glucose cotransporter-2 (SGLT2) inhibitors, which improve outcome in HFrEF, have been shown to increase plasma GDF-15 in diabetic patients. We aimed to investigate the effect of empagliflozin on GDF-15 in HFrEF patients.MethodsThis Empire HF Biomarker substudy was from the multicentre, randomized, double-blind, placebo-controlled Empire HF trial that included 190 patients from June 29, 2017, to September 10, 2019. Stable ambulatory HFrEF patients with ejection fraction of ≤ 40% were randomly assigned (1:1) to empagliflozin 10 mg once daily, or matching placebo for 12 weeks. Changes from baseline to 12 weeks in plasma levels of GDF-15, high-sensitive C-reactive protein (hsCRP), and high-sensitive troponin T (hsTNT) were assessed.ResultsA total of 187 patients who were included in this study, mean age was 64 ± 11 years; 85% male, 12% with type 2 diabetes, mean ejection fraction 29 ± 8, with no differences between the groups. Baseline median plasma GDF-15 was 1189 (918–1720) pg/mL with empagliflozin, and 1299 (952–1823) pg/mL for placebo. Empagliflozin increased plasma GDF-15 compared to placebo (adjusted between-groups treatment effect; ratio of change (1·09 [95% confidence interval (CI), 1.03–1.15]: p = 0.0040). The increase in plasma GDF15 was inversely associated with a decrease in left ventricular end-systolic (R = – 0.23, p = 0.031), and end-diastolic volume (R = – 0.29, p = 0.0066). There was no change in plasma hsCRP (1.09 [95%CI, 0.86–1.38]: p = 0.48) or plasma hsTNT (1.07 [95%CI, 0.97–1.19]: p = 0.18) compared to placebo. Patients with diabetes and treated with metformin demonstrated no increase in plasma GDF-15 with empagliflozin, p for interaction = 0·01.ConclusionEmpagliflozin increased plasma levels of GDF-15 in patients with HFrEF, with no concomitant increase in hsTNT nor hsCRP.Trial registration: The Empire HF trial is registered with ClinicalTrials.gov, NCT03198585.

【 授权许可】

CC BY