Characterization of serum phosphate levels over time with intravenous ferric carboxymaltose versus placebo as treatment for heart failure with reduced ejection fraction and iron deficiency: An exploratory prospective substudy from HEART-FID

Eur J Heart Fail. 2025 May;27(5):872-880. doi: 10.1002/ejhf.3348. Epub 2024 Jun 19.

Abstract

Aims: Ferric carboxymaltose (FCM) is guideline-recommended for iron deficiency (ID) in heart failure with reduced ejection fraction (HFrEF). Despite a well-established safety profile, the magnitude and clinical significance of FCM-induced hypophosphataemia in HFrEF remains unclear. This pre-specified substudy of HEART-FID evaluated serum phosphate, 1,25-dihydroxyvitamin D, and plasma parathyroid hormone (PTH) subsequent to FCM.

Methods and results: HEART-FID was a randomized, double-blind, placebo-controlled trial of ambulatory patients with HFrEF and ID randomized to FCM versus placebo. This substudy assessed mean change from baseline across eight visits over 6 months for the following endpoints: serum phosphate, 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, and PTH, in addition to the clinical severity of potential hypophosphataemia. Overall, 133 patients (n = 62 FCM, n = 71 placebo) were prospectively enrolled. Mean age was 68 ± 11 years, 55 (41.4%) were women, and 29 (21.8%) had chronic kidney disease. Phosphate levels decreased in 34 (57.6%) patients in the FCM group compared with 7 (10.3%) in the placebo group. Mean change in phosphate levels reached a nadir at day 21 (-0.36 ± 0.27 mmol/L) subsequent to FCM infusion with 28 (51%) having moderate-to-severe hypophosphataemia. Reductions in 1,25-dihydroxyvitamin D were also observed, whilst PTH increased. These biochemical changes returned to baseline levels by day 91. Serum levels of 25-hydroxyvitamin D remained stable throughout the study. No serious adverse events associated with hypophosphataemia were reported.

Conclusions: Transient moderate-to-severe hypophosphataemia was frequent subsequent to FCM infusion, accompanied by 1,25-dihydroxyvitamin D decrease and PTH increase. Serum levels of 25-hydroxyvitamin D remained stable. No evidence of symptomatic hypophosphataemia was reported, collectively indicating FCM-related hypophosphataemia to be clinically benign and transient in HFrEF.

Keywords: Ferric carboxymaltose; Heart failure with reduced ejection fraction; Hypophosphataemia.

Publication types

  • Randomized Controlled Trial
  • Multicenter Study

MeSH terms

  • Aged
  • Anemia, Iron-Deficiency* / blood
  • Anemia, Iron-Deficiency* / complications
  • Anemia, Iron-Deficiency* / drug therapy
  • Anemia, Iron-Deficiency* / etiology
  • Double-Blind Method
  • Female
  • Ferric Compounds* / administration & dosage
  • Ferric Compounds* / adverse effects
  • Heart Failure* / blood
  • Heart Failure* / complications
  • Heart Failure* / drug therapy
  • Heart Failure* / physiopathology
  • Humans
  • Hypophosphatemia* / blood
  • Hypophosphatemia* / chemically induced
  • Iron Deficiencies
  • Male
  • Maltose* / administration & dosage
  • Maltose* / adverse effects
  • Maltose* / analogs & derivatives
  • Middle Aged
  • Parathyroid Hormone / blood
  • Phosphates* / blood
  • Prospective Studies
  • Stroke Volume* / physiology
  • Treatment Outcome
  • Vitamin D / analogs & derivatives
  • Vitamin D / blood

Substances

  • ferric carboxymaltose
  • Ferric Compounds
  • Maltose
  • Phosphates
  • Vitamin D
  • Parathyroid Hormone
  • 1,25-dihydroxyvitamin D
  • 25-hydroxyvitamin D