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 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.