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. 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. Data sources 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.

Iron deficiency: new insights into diagnosis and treatment

“…Thus, it is not unexpected that hemoglobin response is better to intravenous than to oral iron, as documented in several studies. 36 One drawback of intravenous iron has been the need for multiple infusions. However, some preparations on the market may replace the total dose needed to correct iron deficiency anemia (up to 1000 mg) in a single or a couple of infusions (Table 4).…”

Iron sucrose – characteristics, efficacy and regulatory aspects of an established treatment of iron deficiency and iron-deficiency anemia in a broad range of therapeutic areas

“…A review of 75 studies (42 of them investigated IS) included a meta-analysis of 24 studies (n = 4400 patients) that suggests an association between i.v. iron and an increased risk of infection (risk ratio 1.33; 95% confidence interval 1.10 --1.64) [95]. However, the authors of this analysis mentioned themselves that their finding might also be a false positive result since infection is generally not a predefined end point and missing data could have created a bias in the analysis.…”

“…iron increases the risk of infections. However, relevant clinical evidence is sparse and inconclusive [81,95,96]. A large multicenter safety study that evaluated an iron status correction and a maintenance IS dosing regimen in 665 hemodialysis patients (covering 8583 doses of 100 mg iron) reported lower rates of infection-related hospitalizations (relative risk 0.54, p < 0.001) and mortality (relative risk 0.61, p = 0.08) compared with a historical general hemodialysis population [81].…”

Impact of a Patient Blood Management Program and an Outpatient Anemia Management Protocol on Red Cell Transfusions in Oncology Inpatients and Outpatients

“…Finally, a concern has been expressed in published studies of a potential negative impact on the occurrence of infection in vulnerable patients when treated with IV iron. Litton et al [21], in their systematic review and metaanalysis of randomized control clinical trials assessing the safety and efficacy of IV iron, found IV iron significantly increased the mean hemoglobin level and decreased the proportion of patients receiving RBC transfusions. They also found that IV iron therapy was associated with a significant increase in the risk of infection (relative risk, 1.33; 95% CI, 1.10-1.64).…”