Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Randomized Controlled Trial
. 2023 Feb;25(2):226-234.
doi: 10.1002/ejhf.2735. Epub 2022 Dec 14.

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

Camilla Fuchs Andersen  1 , Massar Omar  2   3 , Andreas Glenthøj  4   5 , Daniel El Fassi  4   5 , Holger J Møller  6   7 , Jørgen A Lindholm Kurtzhals  8 , Bjarne Styrishave  9 , Caroline Kistorp  5   10 , Christian Tuxen  11 , Mikael K Poulsen  2 , Jens Faber  5   12 , Lars Køber  5   12 , Finn Gustafsson  5   13 , Jacob E Møller  2   13   14 , Morten Schou  1   5 , Jesper Jensen  1
Affiliations
Free article
Randomized Controlled Trial

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

Camilla Fuchs Andersen et al. Eur J Heart Fail. 2023 Feb.
Free article

Abstract

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 (pinteraction >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.

Keywords: Erythropoiesis; Heart failure; Pharmacotherapy; SGLT2 inhibitor.

PubMed Disclaimer

Comment in

References

    1. Zannad F, Ferreira J, Pocock S, Anker SD, Butler J, Filippatos G, et al. SGLT2 inhibitors in patients with heart failure with reduced ejection fraction: a meta-analysis of the EMPEROR-Reduced and DAPA-HF trials. Lancet. 2020;396:819-29.
    1. Jensen J, Omar M, Kistorp C, Gustafsson F, Køber L, Møller JE, et al. Sodium-glucose co-transporter-2 inhibitors in heart failure with reduced ejection fraction: current evidence and future perspectives. Basic Clin Pharmacol Toxicol. 2022;131:5-17.
    1. McMurray JJV, Solomon SD, Inzucchi SE, Køber L, Kosiborod MN, Martinez FA, et al.; DAPA-HF Trial Committees and Investigators. Dapagliflozin in patients with heart failure and reduced ejection fraction. N Engl J Med. 2019;381:1995-2008.
    1. Packer M, Anker SD, Butler J, Filippatos G, Pocock SJ, Carson P, et al.; EMPEROR-Reduced Trial Investigators. Cardiovascular and renal outcomes with empagliflozin in heart failure. N Engl J Med. 2020;383:1413-24.
    1. Griffin M, Rao VS, Ivey-Miranda J, Fleming J, Mahoney D, Maulion C, et al. Empagliflozin in heart failure: diuretic and cardiorenal effects. Circulation. 2020;142:1028-39.

Publication types

Substances