The Efficacy and Safety of Iron Supplementation in Patients With Heart Failure and Iron Deficiency: A Systematic Review and Meta-analysis

Background: Iron deficiency (ID) is a common comorbidity in patients with heart failure (HF) and has been associated with increased mortality and hospitalizations. However, the benefit and safety of iron supplementation in treating HF and ID in randomized controlled trials (RCTs) are inconclusive. We therefore performed a meta-analysis to overcome this limitation. Methods: PubMed, the Cochrane Library, and ClinicalTrials.gov were systematically searched for eligible trials up to December 31, 2014. We also searched the references of all relevant studies and reviews for more trials. Only RCTs reporting the clinical impact of iron therapy in patients with HF with ID compared with no iron treatment were enrolled in our meta-analysis. Results: Five clinical trials comprising a total of 907 patients were finally included. Compared with placebo or no treatment, additional iron therapy was associated with a significantly reduced rate of hospitalization for HF (odds ratio [OR], 0.28; 95% confidence interval [CI], 0.16-0.49), though all-cause mortality was not significantly different (OR, 0.81; 95% CI, 0.42-1.57). In 4 studies where these endpoints were combined, the incidence of hospitalization for HF and death was lowered in the iron supplementation group (OR, 0.47; 95% CI, 0.29-0.76). There was no increase in the risk of adverse events. Conclusions: Iron supplementation significantly reduced the risk of (a) hospitalization for HF and (b) the combined endpoint of hospitalization for HF and death, without increasing the risk of adverse events in patients with symptomatic systolic HF and ID. However, the current data are inadequate to make a clear determination upon mortality.