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Efficacy and safety of iron therapy in patients with chronic heart failure and iron deficiency: a systematic review and meta-analysis based on 15 randomised controlled trials
  1. Junyi Zhang,
  2. Shengda Hu,
  3. Yufeng Jiang,
  4. Yafeng Zhou
  1. Department of Cardiology, The First Affilisted Hospital of Soochow University, Suzhou, Jiangsu, China
  1. Correspondence to Dr Yafeng Zhou, Suzhou, China; zhouyafeng73{at}


Trials studying iron administration in patients with chronic heart failure (CHF) and iron deficiency (ID) have sprung up these years but the results remain inconsistent. The aim of this meta-analysis was to comprehensively evaluate the efficacy and safety of iron therapy in patients with CHF and ID. A literature search was conducted across PubMed, Embase, Cochrane Library, OVID and Web of Science up to 31 July 2019 to search for randomised controlled trials (RCT) comparing iron therapy with placebo in CHF with ID, regardless of presence of anaemia. Published studies reporting data of any of the following outcomes were included: all-cause death, cardiovascular hospitalisation, adverse events, New York Heart Association (NYHA) functional class, left ventricular ejection fraction (LVEF), N-terminal pro b-type natriuretic peptide, peak oxygen consumption, 6 min walking test (6MWT) distance and quality of life (QoL) parameters. 15 RCTs with a total of 1627 patients (911 in iron therapy and 716 in control) were included. Iron therapy was demonstrated to reduce the risk of cardiovascular hospitalisation (OR 0.35, 95% CI 0.12 to 0.99, p=0.049), but was ineffective in reducing all-cause death (OR 0.59, 95% CI 0.33 to 1.06, p=0.078) or cardiovascular death (OR 0.80, 95% CI 0.39 to 1.63, p=0.540). Iron therapy resulted in a reduction in NYHA class (mean difference (MD) −0.73, 95% CI −0.99 to −0.47, p<0.001), an increase in LVEF (MD +4.35, 95% CI 0.69 to 8.00, p=0.020), 6MWT distance (MD +35.44, 95% CI 11.55 to 59.33, p=0.004) and an improvement in QoL: EQ-5D score (MD +4.07, 95% CI 0.84 to 7.31, p=0.014); Minnesota Living With Heart Failure Questionnaire score (MD −19.47, 95% CI −23.36 to −15.59, p<0.001) and Patients Global Assessment (PGA) scale (MD 0.71, 95% CI 0.32 to 1.10, p<0.001). There was no significant difference in adverse events or serious adverse events between iron treatment group and control group. Iron therapy reduces cardiovascular hospitalisation in patients with CHF with ID, and additionally improves cardiac function, exercise capacity and QoL in patients with CHF with ID and anaemia, without an increase of adverse events.

  • heart failure
  • other metabolic (eg, iron, porphyria)
  • clinical physiology

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  • JZ and SH contributed equally.

  • Contributors JZ planned the study, JZ and SH searched the studies, extracted the data, did the statistical analysis and wrote the manuscript. YJ submitted the study. YZ is responsible for the overall content as guarantor.

  • Funding This work was supported by grants from National Natural Science Foundation of China (81873486, 81770327), Natural Scientific Fund of Jiangsu Province (BK20161226), Jiangsu Province’s Key Provincial Talents Program (ZDRCA2016043), Jiangsu Province’s 333 High-Level Talents Project (BRA2017539), Jiangsu Provincial Medical Innovation Team (NO.CXTDA2017009).

  • Disclaimer The funders had no roles in study design, data collection and analysis, decision to publish or preparation of the manuscript.

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Provenance and peer review Not commissioned; externally peer reviewed.