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

Nina Nouhravesh; Jyotsna Garg; Frank W Rockhold; Carmine G De Pasquale; Eileen O'Meara; Gregory D Lewis; Javed Butler; Josephine Harrington; Justin A Ezekowitz; Piotr Ponikowski; Richard W Troughton; Yee Weng Wong; Nicole Blackman; Syed Numan; Robert Adamczyk; Adrian F Hernandez; Robert J Mentz

doi:10.1002/ejhf.3348

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. 2024 Jun 19. doi: 10.1002/ejhf.3348. Online ahead of print.

Authors

Nina Nouhravesh^{1

2}, Jyotsna Garg¹, Frank W Rockhold¹, Carmine G De Pasquale³, Eileen O'Meara⁴, Gregory D Lewis⁵, Javed Butler⁶, Josephine Harrington¹, Justin A Ezekowitz⁷, Piotr Ponikowski⁸, Richard W Troughton⁹, Yee Weng Wong¹⁰, Nicole Blackman¹¹, Syed Numan¹¹, Robert Adamczyk¹¹, Adrian F Hernandez¹, Robert J Mentz¹

Affiliations

¹ Duke Clinical Research Institute, Durham, NC, USA.
² Department of Cardiology, Herlev-Gentofte University Hospital, Copenhagen, Denmark.
³ Flinders Medical Centre, Adelaide, SA, Australia.
⁴ Montreal Heart Institute and Université de Montréal, Quebec, Canada.
⁵ Division of Cardiology, Massachusetts General Hospital, Boston, MA, USA.
⁶ Department of Medicine, University of Mississippi, Jackson, MS, USA.
⁷ Canadian VIGOUR Centre, University of Alberta, Edmonton, AB, Canada.
⁸ The Center for Heart Diseases, University Hospital, Wroclaw Medical University, Wroclaw, Poland.
⁹ Department of Medicine, Christchurch Heart Institute, University of Otago, Christchurch, New Zealand.
¹⁰ Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN, USA.
¹¹ American Regent, Shirley, NY, USA.

PMID: 38896006
DOI: 10.1002/ejhf.3348

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.

Abstract

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