Erythropoietic response after intravenous iron in patients with heart failure and reduced ejection fraction with and without background treatment with sodium-glucose cotransporter 2 inhibitors

Eur J Heart Fail. 2023 Dec;25(12):2191-2198. doi: 10.1002/ejhf.2992. Epub 2023 Aug 24.

Abstract

Aims: Intravenous (IV) iron increases haemoglobin/haematocrit and improves outcomes in patients with heart failure with reduced ejection fraction (HFrEF) and iron deficiency. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) also increase haemoglobin/haematocrit and improve outcomes in heart failure by mechanisms linked to nutrient deprivation signalling and reduction of inflammation and oxidative stress. The effect of IV iron among patients using SGLT2i has not yet been studied. The aim of this study was to evaluate the changes in haemoglobin, haematocrit, and iron biomarkers in HFrEF patients treated with IV iron with and without background SGLT2i treatment. Secondary outcomes included changes in natriuretic peptides, kidney function and heart failure-associated outcomes.

Methods and results: Retrospective, single-centre analysis of HFrEF patients with iron deficiency treated with IV iron using (n = 60) and not using (n = 60) SGLT2i, matched for age and sex. Mean age was 73 ± 12 years, 48% were men, with more than 65% of patients having chronic kidney disease and anaemia. After adjustment for all baseline differences, SGLT2i users experienced a greater increase in haemoglobin and haematocrit compared to SGLT2i non-users: haemoglobin +0.57 g/dl (95% confidence interval [CI] 0.04-1.10, p = 0.036) and haematocrit +1.64% (95% CI 0.18-3.11, p = 0.029). No significant differences were noted for iron biomarkers or any of the secondary outcomes.

Conclusion: Combined treatment with IV iron and background SGLT2i was associated with a greater increase in haemoglobin and haematocrit than IV iron without background SGLT2i. These results suggest that in HFrEF patients treated with IV iron, SGLT2i may increase the erythropoietic response. Further studies are needed to ascertain the potential benefit or harm of combining these two treatments in heart failure patients.

Keywords: Erythropoietic response; Intravenous iron; Sodium-glucose cotransporter 2 inhibitors.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Biomarkers
  • Diabetes Mellitus, Type 2* / complications
  • Diabetes Mellitus, Type 2* / drug therapy
  • Female
  • Glucose
  • Heart Failure* / complications
  • Heart Failure* / drug therapy
  • Hemoglobins
  • Humans
  • Iron
  • Iron Deficiencies*
  • Male
  • Middle Aged
  • Retrospective Studies
  • Sodium
  • Stroke Volume

Substances

  • Iron
  • Biomarkers
  • Hemoglobins
  • Glucose
  • Sodium