Intravenous Iron Decreases Rehospitalizations but Doesn’t Change mortality in Patients Admitted with Acute Heart Failure and Iron Deficiency: A Systematic review and Meta-analysis

Introduction The role of intravenous (IV) iron in chronic heart failure has been well studied, however, its role in acute heart failure (AHF) is less well-known. Including the recent AFFIRM-HF trial, we performed a systematic review and meta-analysis to highlight the role of IV iron in AHF with iron deficiency. Hypothesis We hypothesized that IV iron doesn’t change mortality or heart failure re-hospitalization rates in patients with AHF with iron deficiency. Methods We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) and cohort studies published from inception till June 30, 2021. We searched PubMed, MEDLINE, EMBASE ( embase.com ), and Cochrane database including only RCTs and Cohort studies. We also included one prospective and one retrospective Cohort studies and two RCTs in our meta-analysis. Eligible studies included adults with AHF, left ventricular ejection fraction less than 40%-50%, and able to receive IV iron therapy. Outcomes included re-hospitalization rates and overall mortality from 30 days to 52 weeks post randomization (in one RCT). We used random-effects model calculating Risk Ratio (RR) with 95% confidence interval (95% CI) using Review Manger 5.4 software. I 2 statistics was used to assess heterogeneity. Results There were total 1561 participants in both groups (IV iron and placebo/control) of four studies. The controls were comparable in both cohort studies and both the RCTs were well matched. Our results showed re-hospitalization in 278 of 833 (33.37%) patients in the IV iron/exposure group and 337 of 728 (0.46%) patients in the placebo/control group. The pooled result showed that the risk of rehospitalization was comparable across both groups (RR 0.85, 95%CI 0.62-1.17; I 2 =45%, P=0.14). However, subgroup analysis, including RCTs only showed that IV iron decreases re-hospitalization rate by 28% compared to placebo (RR 0.72, 95% CI: 0.64, 0.82, I 2 =0%, P<0.00001) but didn’t improve mortality when compared to placebo (RR 0.97, 95% CI: 0.73, 1.30, I 2 =0%). Conclusions IV iron showed significant improvement in re-hospitalization rate for AHF hospitalizations in iron deficient patients but didn’t improve overall mortality. We need larger RCTs to further validate its effect on mortality.