Infection risk and clinical outcomes with intravenous iron in adults with heart failure and iron deficiency: a systematic review and meta-analysis of randomised controlled trials

Background Intravenous iron may improve symptoms and reduce heart-failure hospitalisation, but its effect on infection risk remains uncertain. We evaluated infection risk and clinical outcomes in adults with heart failure and iron deficiency.Methods We searched MEDLINE, Embase and Scopus from inception to 16 April 2026, with registry and regulatory searches through 18 October 2026. Randomised controlled trials comparing intravenous iron with placebo, usual care or oral iron were eligible. Participants experiencing infection and infection episodes were analysed separately using random-effects binomial-normal and Poisson-normal models, respectively. Common-effect models were prioritised for mortality and hospitalisation, with random-effects sensitivity analyses. Risk of bias and certainty were assessed using Risk of Bias 2 and Grading of Recommendations Assessment, Development and Evaluation.Results Nineteen reports represented 18 independent cohorts. Three trials contributed participant-level data for any infection (1873 participants; OR 0.82, 95% CI 0.64 to 1.08; low certainty), and three contributed data for serious infection (1890 participants; OR 0.83, 95% CI 0.51 to 1.21; very low certainty). Infection-episode analyses were inconclusive: episode-burden ratios were 1.07 (95% CI 0.76 to 1.86; four trials) for any infection and 1.11 (0.82 to 1.42; seven trials) for serious infection, both with very low GRADE certainty. Intravenous iron probably reduced total first and recurrent heart-failure hospitalisations (three trials; rate ratio 0.78, 95% CI 0.67 to 0.90; moderate certainty). Intravenous iron probably has little or no effect on all-cause mortality (six trials; HR 0.93, 95% CI 0.84 to 1.03; moderate certainty). Quality-of-life findings generally favoured intravenous iron, but differences in instruments, score types and assessment times precluded pooling.Conclusions Intravenous iron probably reduces heart-failure related hospitalisations. No clear increase in infection was observed. Incomplete reporting, inconsistent ascertainment and sparse data limit inference about infection safety. Future trials should prespecify standardised infection outcomes, and report affected participants, recurrent events and person-time.PROSPERO registration number CRD420261355349.