PMID- 36377106
OWN - NLM
STAT- MEDLINE
DCOM- 20230227
LR  - 20230501
IS  - 1879-0844 (Electronic)
IS  - 1388-9842 (Linking)
VI  - 25
IP  - 2
DP  - 2023 Feb
TI  - Effects of empagliflozin on erythropoiesis in heart failure: data from the Empire 
      HF trial.
PG  - 226-234
LID - 10.1002/ejhf.2735 [doi]
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 (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.
CI  - (c) 2022 The Authors. European Journal of Heart Failure published by John Wiley & 
      Sons Ltd on behalf of European Society of Cardiology.
FAU - Fuchs Andersen, Camilla
AU  - Fuchs Andersen C
AUID- ORCID: 0000-0003-3151-5499
AD  - Department of Cardiology, Herlev and Gentofte University Hospital, Herlev, 
      Denmark.
FAU - Omar, Massar
AU  - Omar M
AD  - Department of Cardiology, Odense University Hospital, Odense, Denmark.
AD  - Steno Diabetes Center Odense, Odense, Denmark.
FAU - Glenthoj, Andreas
AU  - Glenthoj A
AD  - Department of Haematology, Centre for Cancer and Organ Diseases, Rigshospitalet, 
      Copenhagen, Denmark.
AD  - Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.
FAU - El Fassi, Daniel
AU  - El Fassi D
AD  - Department of Haematology, Centre for Cancer and Organ Diseases, Rigshospitalet, 
      Copenhagen, Denmark.
AD  - Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.
FAU - Moller, Holger J
AU  - Moller HJ
AD  - Department of Clinical Biochemistry, Aarhus University Hospital, Aarhus, Denmark.
AD  - Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.
FAU - Lindholm Kurtzhals, Jorgen A
AU  - Lindholm Kurtzhals JA
AD  - Department of Clinical Microbiology, Centre of Medical Parasitology, Copenhagen 
      University Hospital, Copenhagen, Denmark.
FAU - Styrishave, Bjarne
AU  - Styrishave B
AD  - Toxicology and Drug Metabolism Group, Department of Pharmacy, University of 
      Copenhagen, Copenhagen, Denmark.
FAU - Kistorp, Caroline
AU  - Kistorp C
AD  - Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.
AD  - Department of Endocrinology, Rigshospitalet, Copenhagen, Denmark.
FAU - Tuxen, Christian
AU  - Tuxen C
AD  - Department of Cardiology, Bispebjerg and Frederiksberg University Hospital, 
      Copenhagen, Denmark.
FAU - Poulsen, Mikael K
AU  - Poulsen MK
AD  - Department of Cardiology, Odense University Hospital, Odense, Denmark.
FAU - Faber, Jens
AU  - Faber J
AD  - Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.
AD  - Department of Internal Medicine, Centre of Endocrinology and Metabolism, Herlev 
      and Gentofte University Hospital, Herlev, Denmark.
FAU - Kober, Lars
AU  - Kober L
AD  - Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.
AD  - Department of Internal Medicine, Centre of Endocrinology and Metabolism, Herlev 
      and Gentofte University Hospital, Herlev, Denmark.
FAU - Gustafsson, Finn
AU  - Gustafsson F
AD  - Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.
AD  - Department of Cardiology, Rigshospitalet, Copenhagen, Denmark.
FAU - Moller, Jacob E
AU  - Moller JE
AD  - Department of Cardiology, Odense University Hospital, Odense, Denmark.
AD  - Department of Cardiology, Rigshospitalet, Copenhagen, Denmark.
AD  - Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark.
FAU - Schou, Morten
AU  - Schou M
AD  - Department of Cardiology, Herlev and Gentofte University Hospital, Herlev, 
      Denmark.
AD  - Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.
FAU - Jensen, Jesper
AU  - Jensen J
AD  - Department of Cardiology, Herlev and Gentofte University Hospital, Herlev, 
      Denmark.
LA  - eng
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20221214
PL  - England
TA  - Eur J Heart Fail
JT  - European journal of heart failure
JID - 100887595
RN  - HDC1R2M35U (empagliflozin)
RN  - 0 (Sodium-Glucose Transporter 2 Inhibitors)
SB  - IM
CIN - Eur J Heart Fail. 2023 Feb;25(2):235-237. PMID: 36597825
CIN - Eur J Heart Fail. 2023 Apr;25(4):598. PMID: 36693808
MH  - Humans
MH  - Male
MH  - *Heart Failure
MH  - Stroke Volume
MH  - Ventricular Function, Left
MH  - *Diabetes Mellitus, Type 2/drug therapy
MH  - Erythropoiesis
MH  - *Sodium-Glucose Transporter 2 Inhibitors/therapeutic use
MH  - *Ventricular Dysfunction, Left/drug therapy
MH  - *Renal Insufficiency, Chronic
OTO - NOTNLM
OT  - Erythropoiesis
OT  - Heart failure
OT  - Pharmacotherapy
OT  - SGLT2 inhibitor
EDAT- 2022/11/16 06:00
MHDA- 2023/03/03 06:00
CRDT- 2022/11/15 01:13
PHST- 2022/10/10 00:00 [revised]
PHST- 2022/08/19 00:00 [received]
PHST- 2022/11/10 00:00 [accepted]
PHST- 2022/11/16 06:00 [pubmed]
PHST- 2023/03/03 06:00 [medline]
PHST- 2022/11/15 01:13 [entrez]
AID - 10.1002/ejhf.2735 [doi]
PST - ppublish
SO  - Eur J Heart Fail. 2023 Feb;25(2):226-234. doi: 10.1002/ejhf.2735. Epub 2022 Dec 
      14.