TY - JOUR
T1 - Effects of Empagliflozin on Erythropoiesis in Heart Failure
T2 - Data from the Empire HF Trial
AU - Fuchs Andersen, Camilla
AU - Omar, Massar
AU - Glenthøj, Andreas
AU - El Fassi, Daniel
AU - Møller, Holger Jon
AU - Lindholm Kurtzhals, Jørgen Anders
AU - Styrishave, Bjarne
AU - Kistorp, Caroline
AU - Tuxen, Christian
AU - Poulsen, Mikael Kjaer
AU - Faber, Jens
AU - Køber, Lars
AU - Gustafsson, Finn
AU - Møller, Jacob Eifer
AU - Schou, Morten
AU - Jensen, Jesper
N1 - This article is protected by copyright. All rights reserved.
PY - 2023/2
Y1 - 2023/2
N2 - 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.
AB - 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.
KW - Diabetes Mellitus, Type 2/drug therapy
KW - Erythropoiesis
KW - Heart Failure
KW - Humans
KW - Male
KW - Renal Insufficiency, Chronic
KW - Sodium-Glucose Transporter 2 Inhibitors/therapeutic use
KW - Stroke Volume
KW - Ventricular Dysfunction, Left/drug therapy
KW - Ventricular Function, Left
KW - Heart failure
KW - Pharmacotherapy
KW - SGLT2 inhibitor
UR - http://www.scopus.com/inward/record.url?scp=85144130941&partnerID=8YFLogxK
U2 - 10.1002/ejhf.2735
DO - 10.1002/ejhf.2735
M3 - Journal article
C2 - 36377106
SN - 1388-9842
VL - 25
SP - 226
EP - 234
JO - European Journal of Heart Failure
JF - European Journal of Heart Failure
IS - 2
ER -