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Meta-Analysis and Metaregression of the Treatment Effect of Intravenous Iron in Iron-Deficient Heart Failure

JACC Heart Fail. 2024 Mar;12(3):525-536 doi: 10.1016/j.jchf.2023.11.006.
PICO Summary
POPULATION:

Patients with iron deficiency and heart failure (HF), (14 randomised controlled trials, n= 6,624).

INTERVENTION:

Intravenous iron (n= 3,407).

COMPARISON:

Placebo (n= 3,217).

OUTCOME:

Treatment with intravenous iron resulted in a lower risk for cardiovascular (CV) death (OR: 0.867; 95% CI [0.755, 0.955]), combined CV death and HF admission (OR: 0.838; 95% CI [0.751, 0.936]), first HF admission (OR: 0.855; 95% CI [0.744, 0.983]), and total HF admissions (rate ratio: 0.739; 95% CI [0.661, 0.827]). Significant heterogeneity among trial results was observed for first and total HF admissions. Meta-regression suggested that some of the heterogeneity was related to the baseline transferrin saturation (TSAT) of the enrolled population, with trials enrolling patients with lower TSAT exhibiting a large effect size on HF-related events.

Abstract
BACKGROUND:

Guidelines recommend that intravenous iron should be considered to improve symptoms of heart failure (HF) and reduce the risk for HF admissions in patients after acute HF.

OBJECTIVES:

This study sought to analyze the effect of intravenous iron on cardiovascular (CV) death and HF admissions in a broad population of HF patients with iron deficiency and the relation with baseline transferrin saturation (TSAT).

METHODS:

A systematic review of all published randomized controlled trials assessing the effect of intravenous iron in patients with iron deficiency and HF between January 1, 2000, and August 26, 2023, was performed. The overall treatment effect was estimated using a fixed effect model for: 1) CV death; 2) CV death and HF admission; 3) first HF admission; and 4) total HF admissions. Metaregression through a mixed effect model was used to explore the impact of baseline TSAT in case of heterogeneity among trial results.

RESULTS:

A total of 14 randomized controlled trials were identified in the systematic review and retained in the meta-analysis. Aggregate-level data were included on 6,624 HF patients, 3,407 of whom were randomized to intravenous iron and 3,217 to placebo. Treatment with intravenous iron resulted in a lower risk for CV death (OR: 0.867 [95% CI: 0.755-0.955]; P = 0.0427), combined CV death and HF admission (OR: 0.838 [95% CI: 0.751-0.936]; P = 0.0015), first HF admission (OR: 0.855 [95% CI: 0.744-0.983]; P = 0.0281), and total HF admissions (rate ratio: 0.739 [95% CI: 0.661-0.827]; P < 0.0001). Significant heterogeneity among trial results was observed for first and total HF admissions. Metaregression suggested that some of the heterogeneity was related to the baseline TSAT of the enrolled population, with trials enrolling patients with lower TSAT exhibiting a large effect size on HF-related events.

CONCLUSIONS:

The totality of data suggests that treatment with intravenous iron reduces both CV death and HF-related events in a broad population with HF. A lower baseline TSAT might be important for the effect on HF-related events.

Metadata
KEYWORDS: evidence-based medicine; heart failure; iron deficiency; meta-analysis
MESH HEADINGS: Humans; Iron; Heart Failure; Quality of Life; Iron Deficiencies; Administration, Intravenous; Randomized Controlled Trials as Topic
Study Details
Study Design: Systematic Review
Language: eng
Credits: Bibliographic data from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine