1. In this randomized controlled trial, ferric carboxymaltose was not superior to placebo in improving death and hospitalization in patients with heart failure with reduced ejection fraction (HFrEF) and concurrent iron deficiency.
2. Ferric carboxymaltose was safe and improved six-minute walk distance.
Evidence Rating Level: 1 (Excellent)
Study Rundown: Iron deficiency is a common complication of heart failure and can exacerbate HFrEF exacerbations. Although oral iron supplementation has not shown benefits for patients with HFrEF and iron deficiency, trials investigating intravenous iron formulations such as ferric carboxymaltose have shown conflicting evidence regarding their impact on mortality and hospitalizations. The current study was a double-blind, randomized, placebo-controlled trial to assess the effects of ferric carboxymaltose on the composite outcome of death, hospitalization, and six-minute walk distance among patients with HFrEF and concurrent iron deficiency. The rates of death and hospitalization for heart failure at 12 months were similar between the ferric carboxymaltose and placebo groups. However, the ferric carboxymaltose resulted in modest improvements in six-minute walk distance compared to placebo at six and 12 months. These results were limited to HFrEF patients, and ferric carboxymaltose could potentially benefit heart failure patients with preserved ejection fraction. Nevertheless, ferric carboxymaltose was non-superior to placebo in its effect on the composite of death, hospitalizations, and six-minute walk distance in patients with HFrEF and concurrent iron deficiency.
Click here to read the study in NEJM
In-Depth [randomized controlled trial]: The current study was a double-blind, randomized, placebo-controlled trial investigating the effects of intravenous ferric carboxymaltose on patients with HFrEF and iron deficiency. Adult patients with heart failure whose left ventricular ejection fraction was 40% or less, whose hemoglobin levels were between 9-13.5 g/dL in men or 9-15 g/dL in women, and who had iron deficiency were eligible for inclusion. Exclusion criteria included recent acute cardiovascular emergencies, hemodialysis, and liver diseases. Overall, 3,065 patients were randomized 1:1 to receive intravenous ferric carboxymaltose or placebo every six months, as guided by their iron indices and hemoglobin levels. The primary outcome was a hierarchical composite of death and hospitalizations for heart failure within 12 months and a change from baseline to six months in the six-minute walk distance test. By 12 months, death had occurred in 8.6% in the ferric carboxymaltose group and 10.3% in the placebo group. The unmatched win ratio for the primary outcome was 1.10 (99% Confidence Interval [CI], 0.99-1.23; p=0.02). The composite of cardiovascular death and hospitalization for heart failure occurred in 31.0% of the ferric carboxymaltose group and 32.2% of the placebo group (hazard ratio, 0.93; 96% CI, 0.81-1.06). The mean (±SD) change from baseline in 6-minute walk distance at 12 months was 5±71m in the ferric carboxymaltose group and 4±72m in the placebo group. The odds of improving by 10m and 20m from baseline at six and 12 months were higher in the ferric carboxymaltose group. The rates of death and serious adverse events were comparable between the two groups. In summary, this trial showed that for ambulatory patients with HFrEF and iron deficiency, intravenous ferric carboxymaltose was not superior to placebo in its impact on the composite of death, hospitalizations for heart failure, and six-minute walk distance.
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