Intravenous Iron Infusion in Patients with Heart Failure: A Systematic Review and Study-Level Meta-Analysis

AIMS: There is considerable variability in the effect of intravenous iron on hard cardiovascular (CV)-related outcomes in patients with heart failure (HF) in randomized controlled trials (RCTs). We use a meta-analytic approach to analyse data from existing RCTs to derive a more robust estimate of the effect size of intravenous iron infusion on CV-related outcomes in patients with HF. METHOD AND RESULTS: PubMed/Medline was searched using the following terms: ('intravenous' and 'iron' and 'heart failure') from inception till 6 November 2022 for RCTs comparing intravenous iron infusion with placebo or standard of care in patients with HF and iron deficiency. Outcomes were the composite of CV mortality and first hospitalization for HF; all-cause mortality; CV mortality; first hospitalization for HF; and total hospitalizations for HF. Random effects risk ratio (RR) with 95% confidence intervals (CIs) were calculated. Ten RCTs with a total of 3438 patients were included. Intravenous iron resulted in a significant reduction in the composite of CV mortality and first hospitalization for HF RR 0.0.85; 95% CI (0.77, 0.95), first hospitalization for HF RR 0.82; 95% CI (0.67, 0.99), and total hospitalizations for HF RR 0.74; 95% CI (0.60, 0.91) but no statistically significant difference in all-cause mortality RR 0.95; 95% CI. (0.83, 1.09) or CV mortality OR 0.89; 95% CI (0.75, 1.05). CONCLUSIONS: Intravenous iron infusion in patients with HF reduces the composite risk of first hospitalization for HF and CV mortality as well as the risks of first and recurrent hospitalizations for HF, with no effect on all-cause mortality or CV mortality alone.