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Intravenous Ferric Carboxymaltose in Heart Failure With Iron Deficiency: The FAIR-HF2 DZHK05 Randomized Clinical
Stefan D Anker1,2, Tim Friede3,4, Javed Butler5,6
1Deutsches Herzzentrum der Charité, Campus Virchow Klinikum, Berlin, Germany.
Insights
Ferric carboxymaltose did not significantly reduce heart failure hospitalizations or cardiovascular death in patients with heart failure and iron deficiency. Further research is needed to clarify the role of intravenous iron therapy in this population.
Area of Science:
- Cardiology
- Hematology
- Clinical Trials
Background:
- Iron deficiency is common in patients with heart failure.
- The efficacy of intravenous iron supplementation in this population remains uncertain.
- Heart failure management often involves addressing comorbidities like iron deficiency.
Purpose of the Study:
- To evaluate the efficacy and safety of ferric carboxymaltose in patients diagnosed with heart failure and iron deficiency.
- To determine if ferric carboxymaltose reduces cardiovascular death or heart failure hospitalizations.
- To assess the impact of ferric carboxymaltose on patients with severe iron deficiency (transferrin saturation <20%).
Main Methods:
- A multicenter, randomized clinical trial involving 1105 patients with heart failure and iron deficiency.
- Participants received either ferric carboxymaltose intravenously or a saline placebo.
- Follow-up was conducted over a median of 16.6 months, assessing primary endpoints including time to cardiovascular death or heart failure hospitalization.
Main Results:
- Ferric carboxymaltose did not significantly reduce the primary endpoint of time to cardiovascular death or first heart failure hospitalization (HR, 0.79; P=.04).
- Total heart failure hospitalizations were also not significantly reduced (RR, 0.80; P=.12).
- No significant difference in serious adverse events was observed between the ferric carboxymaltose and placebo groups.
Conclusions:
- Ferric carboxymaltose did not demonstrate a significant benefit in reducing cardiovascular death or heart failure hospitalizations in the overall cohort.
- The treatment also did not show significant efficacy in patients with transferrin saturation below 20%.
- The safety profile of ferric carboxymaltose was comparable to placebo in this study population.
Importance:
Uncertainty remains about the efficacy of intravenous iron in patients with heart failure and iron deficiency.
Objective:
To assess the efficacy and safety of ferric carboxymaltose in patients with heart failure and iron deficiency.
Design, Setting, And Participants:
This multicenter, randomized clinical trial enrolled 1105 patients with heart failure (defined as having a left ventricular ejection fraction of ≤45%) and iron deficiency (serum ferritin level <100 ng/mL; or if transferrin saturation was <20%, a serum ferritin level between 100 ng/mL and 299 ng/mL) at 70 clinic sites in 6 European countries from March 2017 to November 2023. The median follow-up was 16.6 months (IQR, 7.9-29.9 months).
Intervention:
Administration of ferric carboxymaltose (n = 558) initially given at an intravenous dose of up to 2000 mg that was followed by 500 mg every 4 months (unless stopping criteria were met) vs a saline placebo (n = 547).
Main Outcomes And Measures:
The primary end point events were (1) time to cardiovascular death or first heart failure hospitalization, (2) total heart failure hospitalizations, and (3) time to cardiovascular death or first heart failure hospitalization in patients with a transferrin saturation less than 20%. All end point events were measured through follow-up. The end points would be considered statistically significant if they fulfilled at least 1 of the following conditions: (1) P ≤ .05 for all 3 of the end point comparisons, (2) P ≤ .025 for 2 of the end point comparisons, or (3) P ≤ .0167 for any of the 3 end point comparisons (Hochberg procedure).
Results:
Of the 1105 participants (mean age, 70 years [SD, 12 years]; 33% were women), cardiovascular death or first heart failure hospitalization (first primary outcome) occurred in 141 in the ferric carboxymaltose group vs 166 in the placebo group (hazard ratio, 0.79 [95% CI, 0.63-0.99]; P = .04). The second primary outcome (total heart failure hospitalizations) occurred 264 times in the ferric carboxymaltose group vs 320 times in the placebo group (rate ratio, 0.80 [95% CI, 0.60-1.06]; P = .12). The third primary outcome (cardiovascular death or first heart failure hospitalization in patients with a transferrin saturation <20%) occurred in 103 patients in the ferric carboxymaltose group vs 128 patients in the placebo group (hazard ratio, 0.79 [95% CI, 0.61-1.02], P = .07). A similar amount of patients had at least 1 serious adverse event in the ferric carboxymaltose group (269; 48.2%) vs in the placebo group (273; 49.9%) (P = .61).
Conclusions And Relevance:
In patients with heart failure and iron deficiency, ferric carboxymaltose did not significantly reduce the time to first heart failure hospitalization or cardiovascular death in the overall cohort or in patients with a transferrin saturation less than 20%, or reduce the total number of heart failure hospitalizations vs placebo.
Trial Registration:
ClinicalTrials.gov Identifier: NCT03036462.
