Systematic review and meta-analysis of intravenous iron therapy for patients with heart failure and iron deficiency

Uncertainty remains about the effect of intravenous (i.v.) iron on outcomes for heart failure (HF) with iron deficiency. In the present study, we summarize the efficacy and safety of i.v. iron from six trials (FAIR-HF, CONFIRM-HF, AFFIRM-AHF, IRONMAN, HEART-FID and FAIR-HF2), including 7,175 patients. In comparison to prior analyses, this meta-analysis added new data from FAIR-HF2, used a harmonized and robust Bayesian approach and included individual participant data from five trials. Patients assigned to i.v. iron, compared with those assigned to placebo, had lower rates for the composite endpoint of recurrent HF hospitalizations and cardiovascular mortality at 12 months (risk ratio (RR) = 0.72 (95% confidence interval (CI) = 0.55-0.89)) and for the complete length of follow-up (RR = 0.81 (95% CI = 0.63-0.97)). Each component of the primary endpoint contributed to the beneficial effect of i.v. iron at both 12 months and the complete length of follow-up: recurrent HF hospitalizations (RR = 0.69 (95% CI = 0.48-0.88) and RR = 0.78 (95% CI = 0.55-0.98), respectively) and cardiovascular mortality (hazard ratio (HR) = 0.80 (95% CI = 0.61-1.03) and HR = 0.87 (95% CI = 0.73-1.04), respectively). All-cause mortality at 12 months and for the complete length of follow-up (HR = 0.82 (95% CI = 0.65-1.03)) and HR = 0.92 (95% CI = 0.80-1.07), respectively, indicated the overall safety of i.v. iron treatment. Treatment effects were greatest in the first year after randomization when the doses of i.v. iron provided are highest. These findings suggest that treating iron deficiency in patients with HF significantly reduces cardiovascular events and also suggests further investigation of optimal dosing of i.v. iron.