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 μg/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. (Intravenous Iron Treatment in Patients With Heart Failure and Iron Deficiency; NCT02642562)