Influence of iron deficiency definition on the efficacy of intravenous iron in heart failure: a meta-analysis of randomized trials.

Background: Intravenous iron improves symptoms in heart failure (HF) with iron deficiency (ID) but failed to consistently show a benefit in cardiovascular outcomes. The ID definition used may influence the response to intravenous iron. The aim of this meta-analysis is to assess the influence of ID definition on the intravenous iron effect in HF.

Methods/results: We performed a random-effects meta-analysis of randomized controlled trials (RCT) on intravenous iron (vs. placebo or standard of care) in patients with HF and ID that provided data on transferrin saturation (TSAT) and ferritin subgroups on the composite outcome of cardiovascular death (CVD) or HF hospitalizations (HFH). The risk ratio (RR) and 95% confidence intervals (95% CI) were extracted on the TSAT (< 20% and ≥ 20%) and ferritin (< 100 ng/mL and ≥ 100 ng/mL) subgroups. Data from four major RCT was collected including a total of more than 5500 patients. In patients with a TSAT < 20%, intravenous iron reduced the composite outcome of CVD or HFH: RR 0.81, 95%CI 0.69-0.94, while in patients with a TSAT ≥ 20% the effect was neutral: RR 0.98, 95%CI 0.79-1.21, interaction, P = 0.05. On the other hand, ferritin levels did not modify the effect of IV iron: ferritin ≥ 100 ng/mL RR 0.84, 95%CI 0.65-1.09, and ferritin < 100 ng/mL RR 0.85, 95%CI 0.74-0.97; interaction, P = 0.96.

Conclusions: Our meta-analysis suggests that the benefit of intravenous iron may be restricted to patients with TSAT < 20% regardless of ferritin levels and supports the single use of TSAT < 20% to identify patients with ID who may benefit from intravenous iron therapy.