Effects of empagliflozin on erythropoiesis in heart failure: data from the Empire HF trial.

Publisher: Wiley Country of Publication: England NLM ID: 100887595 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1879-0844 (Electronic) Linking ISSN: 13889842 NLM ISO Abbreviation: Eur J Heart Fail Subsets: MEDLINE

Publication: 2014- : Chichester : Wiley
Original Publication: Amsterdam ; New York : Elsevier Science, c1999-

Heart Failure* ; Diabetes Mellitus, Type 2*/drug therapy ; Sodium-Glucose Transporter 2 Inhibitors*/therapeutic use ; Ventricular Dysfunction, Left*/drug therapy ; Renal Insufficiency, Chronic*; Humans ; Male ; Stroke Volume ; Ventricular Function, Left ; Erythropoiesis

Aims: It remains unknown whether the consistently observed increase in haematocrit with sodium-glucose cotransporter 2 inhibitors is caused by diuresis-associated haemoconcentration or increased erythropoiesis. We aimed to investigate the early effect of empagliflozin on erythropoiesis and iron metabolism in patients with heart failure with reduced ejection fraction (HFrEF).
Methods and Results: The Empire HF was a double-blind, randomized, placebo-controlled trial. Patients with a left ventricular ejection fraction (LVEF) ≤40%, New York Heart Association (NYHA) class I-III symptoms, and on stable guideline-directed HFrEF therapy were randomly assigned (1:1) to empagliflozin or matching placebo once daily for 12 weeks. Exploratory outcomes reflecting changes in erythropoiesis and iron metabolism were analysed. In total, 190 patients were randomized. Baseline characteristics were well-balanced between the groups (age: mean 64 [± 11] years; male: 85%; LVEF: mean 29 [± 8)%; NYHA class II: 78%; type 2 diabetes: 13%; anaemia: 28%; chronic kidney disease: 13%). In this post hoc analysis, erythropoietin was increased with empagliflozin compared to placebo from baseline to 12 weeks (adjusted mean difference 2.6 IU/L, 95% confidence interval [CI] 0.8-4.4; p = 0.0046). Moreover, hepcidin was reduced (adjusted ratio of change 0.76, 95% CI 0.59-0.97; p = 0.031), with no change observed for erythroferrone (adjusted ratio of change 1.17, 95% CI 0.86-1.60; p = 0.31) compared to placebo. No significant treatment-by-subgroup interactions were observed regarding baseline type 2 diabetes, anaemia, or chronic kidney disease (p interaction  >0.05).
Conclusion: These findings suggest that empagliflozin increases erythropoiesis and augments early iron utilization in patients with HFrEF. These mechanisms may contribute to the cardioprotective properties of empagliflozin.
(© 2022 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Comment in: Eur J Heart Fail. 2023 Feb;25(2):235-237. (PMID: 36597825)
Comment in: Eur J Heart Fail. 2023 Apr;25(4):598. (PMID: 36693808)

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Keywords: Erythropoiesis; Heart failure; Pharmacotherapy; SGLT2 inhibitor

HDC1R2M35U (empagliflozin)
0 (Sodium-Glucose Transporter 2 Inhibitors)

Date Created: 20221115 Date Completed: 20230227 Latest Revision: 20230501

20230502

10.1002/ejhf.2735

36377106