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Treatment Effect of IV Iron in Iron-Deficient Heart Failure
Quick Takes
- In patients with HF and iron deficiency, treatment with IV iron can reduce CV deaths and HF hospitalizations.
- The reductions in HF hospitalization are influenced by baseline transferrin saturation (TSAT) levels, with greater benefit accruing to patients with lower baseline TSAT level.
Study Questions:
Is intravenous (IV) iron beneficial for patients with heart failure (HF) and iron deficiency?
Methods:
The investigators conducted a literature search for randomized controlled trials (RCTs) and trials published in English between January 2000 and August 2023, limited to studies comparing IV iron versus placebo in patients with iron deficiency and HF. Trials with cardiac transplant recipients or those using oral iron were excluded. Trial bias was assessed using the Cochrane risk-of-bias tool for RCTs. There were four primary efficacy endpoints for data extraction: cardiovascular (CV) death, the combined endpoint of CV mortality and heart failure hospitalization (HFH), first HFH, and total HFH. A fixed-effects model was used for the primary analysis. The effect size estimate was an odds ratio (OR) with 95% confidence intervals (CIs). For recurrent events, a rate ratio (RR) with 95% CIs was used.
Results:
The meta-analysis included 14 RCTs. Data from 6,624 participants were included, with 3,407 treated with IV iron and 3,217 with placebo. In nine of the trials, the treatment was ferric carboxymaltose. Other forms of IV iron were used in four trials, and one trial used a combination of ferric carboxymaltose and iron sucrose. The effect of treatment with IV iron was described as borderline for CV death (OR, 0.867; 95% CI, 0.755-0.995; p = 0.0427). Its effect on the combined endpoint of CV death and HFH was statistically significant (OR, 0.838; 95% CI, 0.751-0.935; p = 0.0015). The effect was significant both with first HFH (OR, 0.855; 95% CI, 0.744-0.983; p = 0.0281) and recurrent HFH (RR, 0.739; 95% CI, 0.661-0.827; p < 0.001).
No treatment interaction was found for trials using ferric carboxymaltose versus nonferric carboxymaltose compounds. A sensitivity analysis, which used a random-effects model, showed similar outcomes, although the effect was more pronounced for the combined endpoint of CV death and HFH (OR, 0.781), first HFH (OR, 0.774), and total HFH (OR, 0.668). Trials of up to 24 weeks in duration showed similar effects compared with those of longer duration. Trials in which the baseline mean TSAT was ≤20% tended to show a reduction in HFH events, whereas those with a higher mean baseline TSAT did not.
Conclusions:
In patients with HF and iron deficiency, treatment with IV iron reduces both CV deaths and HFH. The reductions in HFH are influenced by baseline transferrin saturation (TSAT) levels, with greater benefit accruing in those with lower baseline TSAT.
Perspective:
The 2022 AHA/ACC/HFSA Guideline for the Management of HF states (Class 2a recommendation): “In patients with HFrEF [heart failure with reduced ejection fraction] and iron deficiency with or without anemia, intravenous iron replacement is reasonable to improve functional status and QOL [quality of life].” Three prior clinical trials (FAIR-HF, CONFIRM-HF, and IRON-HF) of IV iron have demonstrated improvement in symptoms and QOL for patients with HF and iron deficiency. One clinical trial (AFFIRM-AHF) has shown a decrease in hospitalizations for HF among patients hospitalized for HF with EF <50% who had iron deficiency and were treated with IV iron. This meta-analysis aimed to analyze the effects of IV iron on CV death and HFH in a broad population of patients with HF and iron deficiency and to assess its efficacy in relation with baseline TSAT. The results are consistent with those of two previous smaller meta-analyses.
Clinical Topics: Heart Failure and Cardiomyopathies, Acute Heart Failure
Keywords: Anemia, Iron-Deficiency, Heart Failure
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