Effect of intravenous iron-carbohydrate complexes in patients with heart failure with reduced ejection fraction and iron deficiency: a meta-analysis of randomized controlled trials

Abstract

Abstract Background Iron deficiency (ID) has been associated with having the potential to cause heart failure as well as worsening heart failure with reduced ejection fraction (HFrEF). Treatment with a target on ID has been shown to lead to improvement in heart failure patient outcomes. In this study, we performed a meta-analysis of the RCTs to more comprehensively evaluate the effectiveness of intravenous iron-carbohydrate complexes in HF patients with ID. Methods We conducted a systematic literature search on MEDLINE and EMBASE. The search terms included "iron," "iron deficiency," "iron complex," "iron-carbohydrate," "iron sucrose," "heart failure," "HFrEF," and "intravenous." Included studies met the following criteria: (i) a study was published in a peer-reviewed journal; (ii) a study design was a randomized controlled trial; (iii) study enrolled patients with HFrEF and ID, and (iv) a study evaluated intravenous iron-carbohydrate complex. The primary outcome was all-cause mortality during the follow-up. The secondary outcomes were cardiovascular (CV) mortality (deaths due to CV causes), CV admission (hospitalizations due to cardiovascular causes), and HF admission (first hospitalizations due to HF or hospitalizations due to HF worsening). Risk ratios (RRs) with 95% confidence intervals (95%CIs) were calculated with the event/total number in each study and synthesized by a random-effects model. Results We identified 926 articles by the initial database search and additional manual search and retrieved the full text of 18 articles for further review. We then excluded 3 sub-analyses of the included trials to avoid patients’ duplications. Finally, we included 15 RCTs with a total of 3,085 patients (the median or mean age, 62–75 years; female, 25-55%; median follow-up duration, 2–141 weeks). Intravenous iron-carbohydrate complexes were associated with lower risks of all-cause mortality, CV mortality, CV admission, and HF admission, though statistical significance was only observed in HF admission (Figure A-D). CV admission and HF admission provided substantial heterogeneity. Conclusion The results of this meta-analysis showed that intravenous iron-carbohydrate complex therapy in patients with HFrEF and ID was beneficial in lowering the risk of hospitalization due to heart failure. Physicians should be aware of the significance of ID when treating patients with HFrEF.