Abstract

<h3>Introduction</h3> The cost of heart failure (HF) continues to be a huge burden on the healthcare system, with recurrent hospitalizations and mortality being major contributors.<sup>1</sup> Iron deficiency (ID) is a commonly undertreated comorbidity in HF patients, despite research showing its association with increased mortality and hospitalization rates.<sup>2</sup> <h3>Objective</h3> We aim to perform a meta-analysis of randomized controlled trials (RCT) assessing the clinical benefits of treating iron deficiency in heart failure patients. <h3>Methods</h3> We searched Pubmed, Cochrane, EMBASE and NIH databases from 2005-2020. The result was limited to RCT's comparing intravenous (IV) iron-only to placebo, in HF patients with ID. We identified 7 RCT's for inclusion.<sup>3-9</sup> Intervention used in selected trials was IV iron (iron sucrose or ferric carboxymaltose). The primary outcome was the incidence of HF hospitalization, and the secondary outcome was all-cause mortality at maximum follow-up time. A random-effects model was used. The bias of included studies was assessed using the Cochrane bias assessment for RCT's. The analysis was performed using Cochrane Revman version 5.3. <h3>Results</h3> Seven studies were included, with 2,164 participants (1,167 IV Iron group, 997 Placebo group). There were no significant differences in the baseline characteristics of the groups. Follow-up time ranged from 12-52 weeks. Compared to placebo, IV iron significantly reduces the odds of HF hospitalization events in HF patients with ID (OR: 0.54; 95% CI: 0.32 to 0.91; p=0.02) [Figure 1]. Rates of all-cause mortality in the IV iron group were no different than in the placebo group (OR: 0.92; 95% CI: 0.68 to 1.24; p=0.60) [Figure 2]. <h3>Conclusion</h3> Treatment with IV iron compared to placebo significantly reduces the incidence of HF hospitalization in HF patients with ID. Conversely, there was no mortality benefit with using IV iron over placebo in HF patients with ID. Our study represents the largest number of meta-analyzed patients and expands on the recent meta-analysis by Osman et al.<sup>10</sup> by including all types of HF (HFpEF and HFrEF) patients. Further study of the use of IV iron with longer follow-up time is needed to further explore the clinical benefits of IV iron in HF patients with ID.

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