137 Efficacy of intravenous ferric derisomaltose in hospitalised and outpatient settings: insights from ironman trial

Background Prior large clinical trials of intravenous (IV) iron for patients with heart failure and have studied either hospitalised patients (e.g. AFFIRM-HF) or outpatients (e.g. HEART-FID). The IRONMAN trial (NCT02642562) included both hospitalised patients and outpatients. There is uncertainty whether or not the efficacy of intravenous iron differs by enrolment setting - hospitalised patients vs outpatients – in patients with HFrEF. Methods IRONMAN was a randomised trial comparing IV ferric derisomaltose (FDI) and usual care with usual care alone in patients with LVEF ≤45% and either a serum ferritin <100 μg/L or transferrin saturation <20%. The primary outcome was cardiovascular (CV) death and heart failure hospitalisation (HFH) (recurrent events). Secondary outcomes included: (a) CV death or HFH (first event); (b) CV death; (c) CV death, MI, stroke, or HFH; (d) all-cause hospitalisation; (e) CV hospitalisation; (f) all-cause death; (g) all-cause death or unplanned hospitalisation; (h) hospitalisation for infection. In this retrospective post-hoc analysis, the treatment effect of FDI on the primary and secondary endpoints was compared across 3 groups according to enrolment setting: (1) hospitalised; (2) recently hospitalised (within 6 months); (3) outpatients (enrolled on the basis of elevated plasma concentrations of natriuretic peptides [NT-proBNP >250 ng/L in sinus rhythm or >1000 ng/L in atrial fibrillation, or BNP >75 ng/L in sinus rhythm or >300 ng/L in atrial fibrillation]). Results Of 1,137 patients randomised, 164 were enrolled in hospital, 208 were recently hospitalised, and 765 were outpatients. Comparing baseline characteristics across the 3 groups, patients enrolled in hospital had the lowest haemoglobin, transferrin saturation, estimated glomerular filtration rate, left ventricular ejection fraction, systolic blood pressure, were least likely to have ischaemic aetiology, and a history of acute coronary syndrome, and the highest (worst) Minnesota Living with Heart Failure Questionnaire scores [table 1]. Patients enrolled in hospital had more than double the rate of primary endpoints compared to outpatients (rate/100 patient-years of 44 in Group 1 usual care arm versus 18 in Group 3 usual care arm). The effect of FDI on the primary endpoint was similar irrespective of where they were enrolled (hospitalised patients rate ratio 0.87 (95% CI 0.51, 1.49); recently hospitalised rate ratio 0.75 (0.48, 1.17); outpatients rate ratio 0.83 (0.63, 1.10), p interaction=0.70) [table 2 and figure 1]. No differences in treatment effect were observed on the individual components of the primary endpoint or secondary endpoints. Conclusion The effect of FDI is similar whether patients were initiated on treatment in hospital wards or outpatient clinics. Conflict of Interest Research grants (AstraZeneca, Boehringer Ingelheim, Roche Diagnostics), Clinical Events Committee (Bayer), Trial Steering Committee (Cytokinetics)