Adjudication of Hospitalizations and Deaths in the IRONMAN Trial of Intravenous Iron for Heart Failure

BACKGROUND Patients with heart failure and iron deficiency have diverse causes for hospitalization and death that might be affected by iron repletion. OBJECTIVES The purpose of this study was to explore causes of hospitalizations and deaths in a randomized trial (IRONMAN) of heart failure comparing intravenous ferric derisomaltose (FDI) (n = 568) and usual care (n = 569). METHODS Patients with heart failure, left ventricular ejection fraction <= 45%, and either transferrin saturation <20% or serum ferritin <100 m g/L were enrolled. Median follow-up was 2.7 years (Q1-Q3: 1.8-3.6 years). A committee adjudicated the main and contributory causes of unplanned hospitalizations and deaths. RRs (rate ratios) for selected recurrent events with 95% CIs are also reported. RESULTS Compared with usual care, patients randomized to FDI had fewer unplanned hospitalizations (RR: 0.83; 95% CI: 0.71-0.97; P = 0.02), with similar reductions in cardiovascular (RR: 0.83; 95% CI: 0.69-1.01) and noncardiovascular (RR: 0.83; 95% CI: 0.67-1.03) hospitalizations, as well as hospitalizations for heart failure (RR: 0.78; 95% CI: 0.60-1.00), respiratory disease (RR: 0.70; 95% CI: 0.53-0.97), or infection (RR: 0.82; 95% CI: 0.66-1.03). Heart failure was the main cause for 26% of hospitalizations and contributed to or complicated a further 12%. Infection caused or contributed to 38% of all hospitalizations, including 27% of heart failure hospitalizations. Patterns of cardiovascular and all-cause mortality were similar for patients assigned to FDI or usual care. CONCLUSIONS In IRONMAN, FDI exerted similar reductions in cardiovascular and noncardiovascular hospitalizations, suggesting that correcting iron deficiency might increase resistance or resilience to a broad range of problems that cause hospitalizations in patients with heart failure.