Oral iron supplementation in patients with heart failure: a systematic review and meta-analysis

Aims: This review aimed to assess whether oral iron supplementation in a chronic heart failure (HF) population with iron deficiency (ID) or mild anaemia is safe and effective according to evidence-based medicine.

Methods: We retrieved 1803 records from the PubMed, Embase, and the Cochrane Library databases from 1 January 1991 to 15 September 2021. The clinical outcome of oral iron supplementation for ID anaemia in patients with HF was the primary endpoint. The primary safety measures included adverse events and all-cause mortality, and efficacy measures included transferrin saturation (Tsat), ferritin levels, and the 6-min walk test (6MWT). The rate ratio (RR) was used to pool the efficacy measures.

Results: Five randomized controlled trials that compared oral iron treatment for patients with the placebo group and included a combined total of 590 participants were analysed. No significant difference was found in all-cause death between oral iron treatment and placebo groups (RR = 0.77; 95% confidence intervals (CI), 0.46-1.29, Z = 0.98; P = 0.33). However, adverse events were not significantly higher in the iron treatment group (RR = 0.83; 95% CI, 0.60-1.16, Z = 1.07; P = 0.28). In addition, ferritin levels and Tsat were slightly increased after iron complex administration in patients with HF but were not statistically significant (ferritin: mean difference [MD] = 2.70, 95% CI, -2.41 to 7.81, Z = 1.04; P = 0.30; Tsat: MD = 27.42, 95% CI, -4.93 to 59.78, Z = 1.66; P = 0.10). No significant difference was found in exercise capacity, as indicated by the 6MWT results (MD = 59.60, 95% CI, -17.89 to 137.08, Z = 1.51; P = 0.13). We also analysed two non-randomized controlled trials with follow-up results showing that oral iron supplementation increased serum iron levels (MD = 28.87, 95% CI, 1.62-56.12, Z = 2.08; P = 0.04).

Conclusions: Based on the current findings, oral iron supplementation can increase serum iron levels in patients with HF and ID or mild anaemia but does not improve Tsat and 6MWT. In addition, oral iron supplementation is relatively safe.