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

Abstract

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 does not 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. I2statistics 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 re-hospitalization was comparable across both groups (RR 0.85, 95%CI 0.62-1.17; I2=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, I2=0%, P<0.00001) but did not improve mortality when compared to placebo (RR 0.97, 95% CI: 0.73, 1.30, I2 =0%). Conclusions: IV iron showed significant improvement in re-hospitalization rate for AHF hospitalizations in iron deficient patients but did not improve overall mortality. We need larger RCTs to further validate its effect on mortality.