Intravenous iron in patients with heart failure and iron deficiency: an updated meta-analysis

Abstract

Aims: For patients with heart failure (HF) and iron deficiency (ID), randomized trials suggest that intravenous (IV) iron reduces hospitalizations for heart failure (HHF), but uncertainty exists about the effects in subgroups and the impact on mortality. We conducted a meta-analysis of randomized trials investigating the effect of IV iron on clinical outcomes in patients with HF.

Methods and results: We identified randomized trials published between 1 January 2000 and 5 November 2022 investigating the effect of IV iron versus standard care/placebo in patients with HF and ID in any clinical setting, regardless of HF phenotype. Trials of oral iron or not in English were not included. The main outcomes of interest were a composite of HHF and cardiovascular death (CVD), on HHF alone and on cardiovascular and all-cause mortality. Ten trials were identified with 3373 participants, of whom 1759 were assigned to IV iron. IV iron reduced the composite of recurrent HHF and CVD (rate ratio 0.75, 95% confidence interval [CI] 0.61-0.93; p < 0.01) and first HHF or CVD (odds ratio [OR] 0.72, 95% CI 0.53-0.99; p = 0.04). Effects on cardiovascular (OR 0.86, 95% CI 0.70-1.05; p = 0.14) and all-cause mortality (OR 0.93, 95% CI 0.78-1.12; p = 0.47) were inconclusive. Results were similar in analyses confined to the first year of follow-up, which was less disrupted by the COVID-19 pandemic. Subgroup analyses found little evidence of heterogeneity for the effect on the primary endpoint, although patients with transferrin saturation <20% (OR 0.67, 95% CI 0.49-0.92) may have benefited more than those with values ≥20% (OR 0.99, 95% CI 0.74-1.30) (heterogeneity p = 0.07).

Conclusion: In patients with HF and ID, this meta-analysis suggests that IV iron reduces the risk of HHF but whether this is associated with a reduction in cardiovascular or all-cause mortality remains inconclusive.

Keywords: Heart failure; IRONMAN; Intravenous iron; Iron deficiency; Meta-analysis.

Figure 1

Random effects: (A) composite of recurrent hospitalization for heart failure or cardiovascular death, and (B) first hospitalization for heart failure or cardiovascular death. CI, confidence interval; IPD, individual patient data; IV, intravenous/interval variable; MH, Mantel–Haenszel; RR, rate ratio; SE, standard error; SoC, standard of care.

Figure 2

Random effects: (A) composite of recurrent hospitalization for heart failure and cardiovascular death at 1 year, (B) recurrent hospitalization for heart failure at 1 year, (C) cardiovascular death at 1 year, and (D) all‐cause death at 1 year. CI, confidence interval; IPD, individual patient data; IV, intravenous/interval variable; MH, Mantel–Haenszel; RR, rate ratio; SE, standard error; SoC, standard of care.

Figure 3

Random effects: (A) recurrent hospitalization for heart failure, (B) cardiovascular death, and (C) all‐cause mortality. CI, confidence interval; IPD, individual patient data; IV, intravenous/interval variable; MH, Mantel–Haenszel; RR, rate ratio; SE, standard error; SoC, standard of care.

Figure 4

Random effects: (A) recurrent hospitalization for heart failure (HHF) and cardiovascular (CV) death by sex, (B) recurrent HHF and CV death by tertiles of age, (C) recurrent HHF and CV death by New York Heart Association (NYHA) class, and (D) recurrent HHF and CV death by tertiles of estimated glomerular filtration rate (eGFR). CI, confidence interval; IV, intravenous/interval variable; RR, rate ratio; SE, standard error; SoC, standard of care.

Figure 5

Random effects: (A) recurrent hospitalization for heart failure (HHF) and cardiovascular (CV) death by tertiles of haemoglobin (Hb), (B) recurrent HHF and CV death by transferrin saturation (TSAT) <20% or ≥20%, (C) recurrent HHF and CV death by tertiles of ferritin, and (D) recurrent HHF and CV death by tertiles of TSAT. CI, confidence interval; IPD, individual patient data; IV, intravenous/interval variable; RR, rate ratio; SE, standard error; SoC, standard of care.

Figure 6

Random effects: (A) recurrent hospitalization for heart failure (HHF) and cardiovascular (CV) death by heart failure diagnosis (new vs. persistent), (B) recurrent HHF and CV death by heart failure aetiology (ischaemic vs. non‐ischaemic). CI, confidence interval; HF, heart failure; IHD, ischaemic heart disease; IV, intravenous/interval variable; RR, rate ratio; SE, standard error; SoC, standard of care.