Department of Cardiology (CVK) of German Heart Center Charité, Institute of Health Center for Regenerative Therapies (BCRT), German Centre for Cardiovascular Research (DZHK), Partner Site Berlin, Charité Universitätsmedizin, Berlin, Germany.
Division of Cardiology, Duke University Medical Center, Durham, NC, USA.
Eur J Heart Fail. 2023 Jul;25(7):1080-1090. doi: 10.1002/ejhf.2860. Epub 2023 May 21.
Iron deficiency is common in patients with heart failure (HF) and reduced ejection fraction (HFrEF) and is associated with a poor prognosis. Whether intravenous iron replacement improves recurrent HF hospitalizations and cardiovascular mortality of these patients is uncertain although several trials were conducted. Moreover, none of the trials were powered to assess the effect of intravenous iron in clinically important subgroups. Therefore, we conducted a Bayesian analysis to derive precise estimates of the effect of intravenous iron replacement on recurrent HF hospitalizations and cardiovascular mortality in iron-deficient HFrEF patients using consistent subgroup definitions across trials.
Individual participant data were used from the FAIR-HF (n = 459), CONFIRM-HF (n = 304) and AFFIRM-AHF (n = 1108) trials. These data were re-analysed following as closely as possible the approach taken in the analyses of IRONMAN (n = 1137), for which study level data were used. Definitions of outcomes and subgroups from the FAIR-HF, CONFIRM-HF and AFFIRM-AHF were matched with those used in IRONMAN. The primary endpoint was recurrent HF hospitalizations and cardiovascular mortality. The analysis of recurrent events was based on rate ratios (RR) derived from the Lin-Wei-Yang-Ying model, and the data were pooled using Bayesian random-effects meta-analysis. Compared with placebo, intravenous iron significantly reduced the rates of recurrent HF hospitalizations and cardiovascular mortality (RR 0.73, 95% credible interval [CI] 0.48-0.99; between-trial heterogeneity tau = 0.16). The pooled treatment effects did not provide evidence for any differential effects for subgroups based on sex (ratio of rate ratios [RRR] 1.49 [95% CI 0.95-2.37], age <69.4 vs. ≥69.4 years) (RRR 0.68 [0.40-1.15]), ischaemic versus non-ischaemic aetiology of HF (RRR 0.73 [0.42-1.33]), transferrin saturation <20% vs. ≥20% (RRR 0.75 [0.40-1.34]), estimated glomerular filtration rate ≤60 versus >60 ml/min/1.73 m (RRR 0.97 [0.56-1.68]), haemoglobin <11.8 versus ≥11.8 (RRR 0.95 [0.53-1.60]), ferritin <35 versus ≥35 μg/L (RRR 1.26 [0.72-2.48]) and New York Heart Association class II versus III/IV (RRR 0.91 [0.54-1.56]).
Treatment of iron-deficient HFrEF patients with intravenous iron - namely with ferric carboxymaltose or ferric derisomaltose - results in significant reduction in recurrent HF hospitalizations and cardiovascular mortality. Results were nominally consistent across the subgroups studied, but for several of these subgroups uncertainty remains present.
铁缺乏症在射血分数降低的心力衰竭（HFrEF）患者中很常见，与预后不良有关。尽管进行了几项试验，但静脉铁替代治疗是否能改善这些患者的复发性心力衰竭住院和心血管死亡率仍不确定。此外，没有一项试验有足够的效力来评估静脉铁在临床上重要亚组中的作用。因此，我们使用一致的试验间亚组定义，通过贝叶斯分析，从 FAIR-HF（n=459）、CONFIRM-HF（n=304）和 AFFIRM-AHF（n=1108）试验中获得静脉铁替代治疗对铁缺乏性 HFrEF 患者复发性心力衰竭住院和心血管死亡率影响的精确估计。
使用 FAIR-HF、CONFIRM-HF 和 AFFIRM-AHF 试验的个体参与者数据。这些数据按照尽可能接近 IRONMAN 分析中采用的方法进行了重新分析（n=1137），其中使用了研究水平的数据。FAIR-HF、CONFIRM-HF 和 AFFIRM-AHF 的结局和亚组定义与 IRONMAN 中使用的定义相匹配。主要终点是复发性心力衰竭住院和心血管死亡率。复发性事件的分析基于 Lin-Wei-Yang-Ying 模型得出的率比（RR），并使用贝叶斯随机效应荟萃分析对数据进行了汇总。与安慰剂相比，静脉铁显著降低了复发性心力衰竭住院和心血管死亡率的发生率（RR 0.73，95%可信区间[CI]0.48-0.99；试验间异质性 tau=0.16）。汇总的治疗效果并没有为基于性别（RRR 1.49[95%CI 0.95-2.37]）、年龄<69.4 岁与≥69.4 岁（RRR 0.68[0.40-1.15]）、心力衰竭的缺血性与非缺血性病因（RRR 0.73[0.42-1.33]）、转铁蛋白饱和度<20%与≥20%（RRR 0.75[0.40-1.34]）、估计肾小球滤过率≤60 与>60ml/min/1.73m（RRR 0.97[0.56-1.68]）、血红蛋白<11.8 与≥11.8（RRR 0.95[0.53-1.60]）、铁蛋白<35 与≥35μg/L（RRR 1.26[0.72-2.48]）和纽约心脏协会（NYHA）心功能分级 II 与 III/IV（RRR 0.91[0.54-1.56]）的亚组提供了证据表明存在差异治疗效果。
静脉铁治疗铁缺乏性射血分数降低的心力衰竭患者（即使用羧基麦芽糖铁或去铁胺麦芽糖铁）可显著降低复发性心力衰竭住院和心血管死亡率。结果在研究的亚组中基本一致，但对于其中的几个亚组，仍存在不确定性。
