From the Division of Cardiology, Department of Medicine (R.J.M., J.H., A.F.H.), and the Department of Biostatistics and Bioinformatics (F.W.R.), Duke University School of Medicine, and Duke Clinical Research Institute (R.J.M., J.G., F.W.R., L.S., J.H., A.F.H.) - both in Durham, NC; Baylor Scott and White Research Institute, Dallas (J.B.); the Department of Medicine, University of Mississippi, Jackson (J.B.); Flinders Medical Centre, Flinders University, Adelaide, SA (C.G.D.P.), and the Department of Cardiology, Prince Charles Hospital and Faculty of Medicine, University of Queensland, Brisbane (Y.W.W.) - both in Australia; Canadian VIGOUR Centre, University of Alberta, Edmonton (J.A.E.), and Montreal Heart Institute and Université de Montréal, Montreal (E.O.) - both in Canada; the Cardiology Division and Cardiovascular Research Center, Massachusetts General Hospital, Boston (G.D.L.); the Center for Heart Diseases, University Hospital, Wroclaw Medical University, Wroclaw, Poland (P.P.); Christchurch Heart Institute, University of Otago, Christchurch, New Zealand (R.W.T.); the Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN (Y.W.W.); and American Regent, Shirley, NY (R.A., N.B.).
N Engl J Med. 2023 Sep 14;389(11):975-986. doi: 10.1056/NEJMoa2304968. Epub 2023 Aug 26.
Ferric carboxymaltose therapy reduces symptoms and improves quality of life in patients who have heart failure with a reduced ejection fraction and iron deficiency. Additional evidence about the effects of ferric carboxymaltose on clinical events is needed.
In this double-blind, randomized trial, we assigned ambulatory patients with heart failure, a left ventricular ejection fraction of 40% or less, and iron deficiency, in a 1:1 ratio, to receive intravenous ferric carboxymaltose or placebo, in addition to standard therapy for heart failure. Ferric carboxymaltose or placebo was given every 6 months as needed on the basis of iron indexes and hemoglobin levels. The primary outcome was a hierarchical composite of death within 12 months after randomization, hospitalizations for heart failure within 12 months after randomization, or change from baseline to 6 months in the 6-minute walk distance. The significance level was set at 0.01.
We enrolled 3065 patients, of whom 1532 were randomly assigned to the ferric carboxymaltose group and 1533 to the placebo group. Death by month 12 occurred in 131 patients (8.6%) in the ferric carboxymaltose group and 158 (10.3%) in the placebo group; a total of 297 and 332 hospitalizations for heart failure, respectively, occurred by month 12; and the mean (±SD) change from baseline to 6 months in the 6-minute walk distance was 8±60 and 4±59 m, respectively (Wilcoxon-Mann-Whitney P = 0.02; unmatched win ratio, 1.10; 99% confidence interval, 0.99 to 1.23). Repeated dosing of ferric carboxymaltose appeared to be safe with an acceptable adverse-event profile in the majority of patients. The number of patients with serious adverse events occurring during the treatment period was similar in the two groups (413 patients [27.0%] in the ferric carboxymaltose group and 401 [26.2%] in the placebo group).
Among ambulatory patients who had heart failure with a reduced ejection fraction and iron deficiency, there was no apparent difference between ferric carboxymaltose and placebo with respect to the hierarchical composite of death, hospitalizations for heart failure, or 6-minute walk distance. (Funded by American Regent, a Daiichi Sankyo Group company; HEART-FID ClinicalTrials.gov number, NCT03037931.).
铁羧基麦芽糖治疗可改善射血分数降低的心力衰竭伴铁缺乏患者的症状并提高其生活质量。需要更多关于铁羧基麦芽糖对临床事件影响的证据。
在这项双盲、随机试验中，我们将射血分数为 40%或更低且铁缺乏的活动性心力衰竭患者按 1:1 的比例随机分为铁羧基麦芽糖组或安慰剂组，两组均在接受心力衰竭标准治疗的基础上，根据铁指标和血红蛋白水平按需每 6 个月静脉给予铁羧基麦芽糖或安慰剂。主要结局是随机分组后 12 个月内的死亡、随机分组后 12 个月内心力衰竭住院或 6 分钟步行距离自基线至 6 个月的变化的分层复合结局。显著性水平设定为 0.01。
我们共纳入了 3065 例患者，其中 1532 例随机分配至铁羧基麦芽糖组，1533 例分配至安慰剂组。铁羧基麦芽糖组有 131 例（8.6%）患者在 12 个月时死亡，安慰剂组有 158 例（10.3%）患者死亡；两组分别有 297 例和 332 例患者在 12 个月时因心力衰竭住院；6 分钟步行距离自基线至 6 个月的平均（±SD）变化分别为 8±60m 和 4±59m（Wilcoxon-Mann-Whitney P=0.02；未配对优势比为 1.10；99%置信区间为 0.99 至 1.23）。大多数患者重复给予铁羧基麦芽糖治疗的安全性良好，不良事件谱可接受。两组治疗期间发生严重不良事件的患者人数相似（铁羧基麦芽糖组 413 例[27.0%]，安慰剂组 401 例[26.2%]）。
在射血分数降低的活动性心力衰竭伴铁缺乏的患者中，与安慰剂相比，铁羧基麦芽糖在死亡、心力衰竭住院或 6 分钟步行距离的分层复合结局方面无明显差异。（由 American Regent，Daiichi Sankyo Group 公司资助；HEART-FID ClinicalTrials.gov 编号：NCT03037931。）
