Supplementary Material for: Effects of Ferric Derisomaltose in Heart Failure with Iron Deficiency According to Renal Function in the IRONMAN Randomised Controlled trial.

Introduction:
For heart failure (HF) with iron deficiency (ID), the benefits of intravenous iron might differ according to kidney function.
Methods:
IRONMAN was a randomised, open-label trial of intravenous ferric derisomaltose (FDI) versus usual care in patients with HF, left ventricular ejection fraction ≤45% and ID, (transferrin saturation <20% and/or ferritin <100µg/L). The primary composite endpoint of recurrent hospitalisation for HF and cardiovascular (CV) death was lower in those assigned to FDI. Analysis according to baseline estimated glomerular filtration rate (eGFR) is now reported, with outcomes assessed in 3 categories of eGFR.
Results:
Of 1,137 patients randomised, eGFR was <45ml/min/1.73m2 for 435 (38%), 45-59ml/min/1.73m2 for 295 (26%), and >60ml/min/1.73m2 for 407 (36%). Patients with eGFR <45ml/min/1.73m2 were older, had more severe HF and more events. For the primary outcome, the primary endpoint rates per 100 patient-years for FDI vs. usual care across eGFR categories were 164 and 213 (rate ratio 0.77 [95%CI 0.57,1.03]), 84 and 105 (RR 0.79 [95%CI 0.51,1.22]), 88 and 93 (RR 0.98 [95%CI 0.62,1.54]) respectively, but no statistically significant interaction between eGFR category and treatment effect was observed (pinteraction= 0.67). When eGFR was <45ml/min/1.73m2, FDI was associated with more favourable effects on Minnesota Living with Heart Failure score at 4-months (p<0.001; pinteraction = 0.01 by eGFR class) and trends to greater reductions in first hospitalisation for HF or CV death (HR 0.76 [95%CI 0.58,0.99]; pinteraction = 0.53) and first hospitalisation for myocardial infarction, stroke or HF, or CV death (HR 0.71 [95%CI 0.55,0.92]; pinteraction = 0.29), although tests for interaction by eGFR class were not significant.
Conclusion:
For patients with HF and ID, those with eGFR <45ml/min/1.73m2 are more symptomatic, have worse outcomes and might receive greater benefit from FDI. Analysis of other randomised trials, ideally an individual patient data meta-analysis, are required to confirm these findings.

引言：
对于合并铁缺乏（ID）的心力衰竭（HF）患者，静脉铁剂的获益可能因肾功能而异。
方法：
IRONMAN是一项针对心力衰竭、左心室射血分数≤45%且合并铁缺乏（转铁蛋白饱和度<20%和/或铁蛋白<100μg/L）患者的随机开放标签试验，比较静脉注射异麦芽糖酐铁（FDI）与常规护理的效果。分配至FDI组的患者，其心力衰竭再住院和心血管（CV）死亡的主要复合终点发生率更低。本文报告了根据基线估计肾小球滤过率（eGFR）进行的分析，将结局按eGFR分为3类评估。
结果：
在1137例随机化患者中，435例（38%）的eGFR<45ml/min/1.73m²，295例（26%）为45-59ml/min/1.73m²，407例（36%）>60ml/min/1.73m²。eGFR<45ml/min/1.73m²的患者年龄更大，心力衰竭更严重，事件发生率更高。对于主要结局，不同eGFR类别中FDI组与常规护理组每100患者年的主要终点发生率分别为：164 vs 213（率比0.77，95%置信区间[0.57,1.03]）、84 vs 105（率比0.79，95%置信区间[0.51,1.22]）、88 vs93（率比0.98，95%置信区间[0.62,1.54]）；但未观察到eGFR类别与治疗效果之间存在统计学显著的交互作用（交互作用p值=0.67）。当eGFR<45ml/min/1.73m²时，FDI对4个月时明尼苏达心力衰竭生活质量评分具有更有利的影响（p<0.001；eGFR类别交互作用p值=0.01），且在首次心力衰竭住院或心血管死亡（风险比（HR，hazard ratio）0.76，95%置信区间[0.58,0.99]；交互作用p值=0.53）以及首次心肌梗死、卒中或心力衰竭住院或心血管死亡（风险比（HR）0.71，95%置信区间[0.55,0.92]；交互作用p值=0.29）方面有更大幅度降低的趋势，尽管eGFR类别交互作用检验无统计学意义。
结论：
对于合并铁缺乏的心力衰竭患者，eGFR<45ml/min/1.73m²者症状更明显，结局更差，且可能从异麦芽糖酐铁（FDI）治疗中获得更大获益。需要对其他随机试验进行分析（理想情况下为个体患者数据荟萃分析）以证实这些发现。