Effects and Safety of Oral Iron for Heart Failure with Iron Deficiency: A Systematic Review and Meta-Analysis with Trial Sequential Analysis

Abstract

Background. Oral iron supplement is commonly prescribed to heart failure patients with iron deficiency. However, the effects of oral iron for heart failure remain controversial. This study included randomized controlled trials (RCTs) for meta-analysis to evaluate the effects of oral iron for heart failure patients. Methods. Nine databases (The Cochrane Library, Embase, PubMed, CINAHL, Web of science, CNKI, SinoMed, VIP, and Wanfang) were searched for RCTs of oral iron for heart failure from inception to October 2021. The effects were assessed with a meta-analysis using Revman 5.3 software. The trial sequential analysis was performed by TSA 0.9.5.10 beta software. The risk of bias of trials was evaluated via Risk of Bias tool. The evidence quality was assessed through GRADE tool. Results. Four studies including 582 patients with heart failure and iron deficiency were enrolled. The results indicated that oral iron treatment could improve left ventricular ejection fraction (LVEF, MD = 1:52%, 95% CI: 0.69 to 2.36, P = 0:0003) and serum ferritin (MD = 1:64, 95% CI: 0.26 to 3.02, P = 0:02). However, there was no between-group difference in the 6-minute walk distances (6MWT), N terminal pro B type natriuretic peptide (NT-proBNP) or hemoglobin level when compared with control group. Subgroup analyses revealed that the effects of oral iron on 6 MWT and serum ferritin could not be affected by duration and frequency of oral iron uptakes. In trial sequential analysis of LVEF and serum ferritin, the Z-curves crossed the traditional boundary and trail sequential monitoring boundary but did not reach the required information size. Conclusion. This analysis showed that oral iron could improve cardiac function measured by LVEF, and iron stores measured serum ferritin, but lack of effect on exercise capacity measured by 6 MWT, and iron stores measured by hemoglobin. Given the overall poor methodological quality and evidence quality, these findings should be treated cautiously.

Effect of oral iron supplementation on functional capacity in heart failure patients

“…4 A systematic review and meta-analysis study conducted by Song, et al, 10 stated that oral iron supplementation did not improve functional capacity in heart failure patients assessed by 6MWT examination (MD=59.6, CI 95%, -17.89 to 137.08, p=0.13). A systematic review and metaanalysis study by Tan, et al, 11 also yielded similar results (MD=13.92 m, 95% CI: -47.33 to 19.5, p=0.41). The high heterogeneity (I2=92%, p heterogeneity<0.000001 and I2=75%, p heterogeneity<0.02) in both studies indicate that the results of the RCTs included in both systematic review and meta-analyses have very mixed results.…”

“…The high heterogeneity (I2=92%, p heterogeneity<0.000001 and I2=75%, p heterogeneity<0.02) in both studies indicate that the results of the RCTs included in both systematic review and meta-analyses have very mixed results. Tan, et al, 11 explained the source of heterogeneity in their study may be due to one study by Jiang, et al, 15 which after eliminated the heterogeneity became low. 12 + + +…”

Guía mexicana de práctica clínica para el diagnóstico y el tratamiento de la insuficiencia cardiaca

“…Una RS publicada en 2022 por Tan et al incluyó 4 ECAs en donde se reportó que la suplementación de hierro oral mejora los valores de la FEVI (DM 1.52%; IC95%: 0.69; 2.36) y de la ferritina sérica (DM 1.64; IC95%: 0.26; 3.02), sin embargo, no hubo diferencias en la evaluación de 6MWT, NT-proBNP; y de los niveles de hemoglobina 146 .…”