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

Abstract

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.

Fig 1 Flow diagram of selection of studies on intravenous iron therapy

Fig 2 Standardised mean difference in haemoglobin (g/L) in patients who received intravenous iron compared with oral iron and no iron. Weights are from random effects analysis

Fig 3 Risk of red blood cell transfusion in patients who received intravenous iron compared with oral iron and no iron. Weights are from random effects analysis

Fig 4 Regression of erythroid stimulating agent on log risk ratio of red blood cell transfusion. Slope of regression line 0.32, 95% confidence interval 0.02 to 0.63; P=0.04)

Fig 5 Risk of infection in patients who received intravenous iron. Weights are from random effects analysis

Fig 6 Odds ratio of transfusion against standard error of log odds ratio