Safety and efficacy of intravenous iron therapy in reducing requirement for allogeneic blood transfusion: systematic review and meta-analysis of randomised clinical trials

OBJECTIVES To evaluate the efficacy and safety of intravenous iron, focusing primarily on its effects on haemoglobin, requirement for transfusion, and risk of infection. DESIGN Systematic review and meta-analysis of randomised controlled trials investigating the safety and efficacy of intravenous iron therapy. DATA SOURCES Randomised controlled trials from Medline, Embase, and the Cochrane Central Register of Controlled Trials from 1966 to June 2013, with no language restrictions. ELIGIBILITY CRITERIA FOR SELECTING STUDIES Eligible trials were randomised controlled trials of intravenous iron compared with either no iron or oral iron. Crossover and observational studies were excluded. MAIN OUTCOME MEASURES Change in haemoglobin concentration and risk of allogeneic red blood cell transfusion (efficacy) and risk of infection (safety). RESULTS Of the 75 trials meeting the inclusion criteria, 72 studies including 10 605 patients provided quantitative outcome data for meta-analysis. Intravenous iron was associated with an increase in haemoglobin concentration (standardised mean difference 6.5 g/L, 95% confidence interval 5.1 g/L to 7.9 g/L) and a reduced risk of requirement for red blood cell transfusion (risk ratio 0.74, 95% confidence interval 0.62 to 0.88), especially when intravenous iron was used with erythroid stimulating agents (ESAs) or in patients with a lower baseline plasma ferritin concentration. There were no significant interactions between the efficacy of intravenous iron and type or dose administered. Intravenous iron was, however, associated with a significant increase in risk of infection (relative risk 1.33, 95% confidence interval 1.10 to 1.64) compared with oral or no iron supplementation. The results remained similar when only high quality trials were analysed. CONCLUSIONS Intravenous iron therapy is effective in increasing haemoglobin concentration and reducing the risk of allogeneic red blood cell transfusion and could have broad applicability to a range of acute care settings. This potential benefit is counterbalanced by a potential increased risk of infection.