Abstract
BACKGROUND: The actual effects of intravenous iron therapy on hospitalizations, mortality and safety in patients with heart failure and iron deficiency remained controversial. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to elucidate the cardiovascular benefits and safety of intravenous iron therapy. METHODS: We searched PubMed, Embase, and Cochrane Library databases for relevant RCTs of intravenous iron therapy in patients with heart failure and iron deficiency published from inception through April 20, 2024. Our primary endpoints of interest were heart failure hospitalizations, all-cause mortality, cardiovascular hospitalizations, and cardiovascular death. Additional risk of treatment complications included infections, administration site conditions, poisoning and procedural complications. We employed the fragility index and the reverse fragility index to further assess the robustness of our meta-analysis results. Additionally, subgroup analyses were conducted to explore potential clinical benefits. RESULTS: Eleven trials encompassing a collective cohort of 6511 participants met our predefined eligibility criteria and were included in our meta-analysis. Intravenous iron therapy yielded a 21% relative reduction in heart failure hospitalizations and cardiovascular death (P<0.01), a 24% relative reduction in heart failure hospitalization (P<0.01) and a 28% relative reduction in cardiovascular hospitalizations and cardiovascular death (P<0.01). The corresponding high fragility indexes showed these pooled results to be robust. Our analysis revealed no statistically significant differences in terms of all-cause mortality (P = 0.11). Subgroup analyses revealed more favorable effects of intravenous iron therapy in trials that had a treatment duration of ≥ 24 weeks. The administration of intravenous iron did not have an additional risk of treatment-related complications (P = 0.93). CONCLUSIONS: Intravenous iron therapy in patients with chronic heart failure and iron deficiency significantly reduced rehospitalization for heart failure and cardiovascular death but was not associated with all-cause mortality. Long-term administration of iron supplements holds significant promise as a routine therapeutic approach for heart failure patients with iron deficiency.