Nouhravesh Nina, Garg Jyotsna, Rockhold Frank W, De Pasquale Carmine G, O'Meara Eileen, Lewis Gregory D, Butler Javed, Harrington Josephine, Ezekowitz Justin A, Ponikowski Piotr, Troughton Richard W, Wong Yee Weng, Blackman Nicole, Numan Syed, Adamczyk Robert, Hernandez Adrian F, Mentz Robert J
Duke Clinical Research Institute, Durham, NC, USA.
Department of Cardiology, Herlev-Gentofte University Hospital, Copenhagen, Denmark.
Eur J Heart Fail. 2025 May;27(5):872-880. doi: 10.1002/ejhf.3348. Epub 2024 Jun 19.
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.
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.
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.
羧麦芽糖铁（FCM）是射血分数降低的心力衰竭（HFrEF）中铁缺乏（ID）的指南推荐用药。尽管其安全性已得到充分确立，但FCM诱导的HFrEF患者低磷血症的程度和临床意义仍不明确。这项HEART - FID的预先指定亚研究评估了FCM治疗后血清磷酸盐、1,25 - 二羟基维生素D和血浆甲状旁腺激素（PTH）的情况。
HEART - FID是一项针对HFrEF和ID门诊患者的随机、双盲、安慰剂对照试验，患者被随机分为FCM组和安慰剂组。该亚研究评估了6个月内8次访视时以下终点指标相对于基线的平均变化：血清磷酸盐、25 - 羟基维生素D、1,25 - 二羟基维生素D和PTH，以及潜在低磷血症的临床严重程度。总体而言，前瞻性纳入了133例患者（FCM组n = 62例，安慰剂组n = 71例）。平均年龄为68±11岁，55例（41.4%）为女性，29例（21.8%）患有慢性肾脏病。FCM组34例（57.6%）患者的磷酸盐水平下降，而安慰剂组为7例（10.3%）。FCM输注后第21天磷酸盐水平的平均变化达到最低点（-0.36±0.27 mmol/L），28例（51%）出现中度至重度低磷血症。还观察到1,25 - 二羟基维生素D降低，而PTH升高。这些生化变化在第91天恢复到基线水平。整个研究过程中25 - 羟基维生素D的血清水平保持稳定。未报告与低磷血症相关的严重不良事件。
FCM输注后经常出现短暂的中度至重度低磷血症，并伴有1,25 - 二羟基维生素D降低和PTH升高。25 - 羟基维生素D的血清水平保持稳定。未报告有症状性低磷血症的证据，总体表明HFrEF中FCM相关的低磷血症在临床上是良性且短暂的。
