Iron deficiency (ID) is a comorbid condition frequently seen in patients with heart failure (HF). Iron has an important role in the transport of oxygen, and is also essential for skeletal and cardiac muscle, which depend on iron for oxygen storage and cellular energy production. Thus, ID per se, even without anaemia, can be harmful. In patients with HF, ID is associated with a poorer quality of life (QoL) and exercise capacity, and a higher risk of hospitalisations and mortality, even in the absence of anaemia.
FAIR-HF [15] |
CONFIRM-HF [17] |
EFFECT-HF [18] |
AFFIRM-AHF [16] |
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Design, duration and number of patients who received treatment per arm |
Double-blind, placebo-controlled, randomised; 24 weeks FCM: 305 Placebo: 154 |
Double-blind, placebo-controlled, randomised; 52 weeks FCM: 152 Placebo: 152 |
Open-label, SoC-controlled, randomised; 24 weeks FCM: 88 SoC: 86 |
Double-blind, placebo-controlled, randomised; 52 weeks FCM: 559 Placebo: 551 |
Key inclusion criteria |
NYHA class II (LVEF ≤ 40%) or III (LVEF ≤45%) Hb 9.5–13.5 g/dL ID (ferritin <100 µg/L or 100–299 µg/L + TSAT <20%) |
NYHA class II/III (LVEF ≤ 45%) BNP >100 pg/mL and/or NT-proBNP >400 pg/ml Hb <15 g/dL ID (ferritin <100 µg/L or 100–300 µg/L + TSAT < 20%) |
NYHA class II/III (LVEF ≤ 45%) BNP >100 pg/mL and/or NT-proBNP >400 pg/ml Hb <15 g/dL ID (ferritin <100 µg/L or 100–300 µg/L + TSAT < 20%) Peak VO2 10–20 mL/kg/min (reproducible) |
Hospitalised for acute HF, treated with at least 40 mg IV furosemide (or equivalent) LVEF < 50% ID (ferritin <100 µg/L or 100–299 µg/L + TSAT <20%) |
Dosing regimen |
Dose determined by Ganzoni formula [50] FCM equivalent to 200 mg iron/week for iron repletion then Q4W for maintenance |
FCM equivalent to 500–3500 mg iron for iron repletion (baseline and Week 6); 500 mg iron for maintenance (Weeks 12, 24, 36) if iron deficiency still present |
FCM equivalent to 500–1000 mg iron for iron repletion (baseline and Week 6) based on screening Hb and weight; only given at Week 6 if <70 kg and Hb <10 g/dL or ≥70 kg and Hb <14 g/dL; 500 mg iron for maintenance (Week 12) if iron deficiency still present |
FCM equivalent to 500–1000 mg at baseline and Week 6 for iron repletion; 500 mg iron for maintenance at Weeks 12 and 24 for patients in whom ID persisted and for whom Hb was 8–15 g/dL |
Mean cumulative iron dose/ total number of injections |
NA/ Median 6 (3–7) during iron repletion phase |
1500 mg/>75% of patients receiving FCM needed 2 injections maximum to correct and sustain iron parameters during the study |
1204 mg/42% received 1, 55% received 2, and 3.3% received 3 FCM administrations |
1352 mg/80% of patients received 1 or 2 FCM administrations during the treatment phase (i.e., up to Week 24) |
Treatment effect on iron-related parameters |
FCM vs. placebo at Week 24 (mean ± SE)
(p < 0.001 for all) |
Mean treatment effect (baseline-adjusted) difference for FCM vs. placebo at Week 52:
(p < 0.001 for all) |
FCM vs. control (SoC) at Week 24:
|
Compared with placebo, serum ferritin and TSAT both rose with FCM by week 6 and continued to be significantly higher at week 52 |
Primary endpoint results |
Changes in PGA and NYHA functional class at Week 24 for FCM vs. placebo
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LS means ± SE 6 MWT distance at Week 24 for FCM vs. placebo
|
Primary analysis LS means change from baseline in peak VO2 at Week 24 for FCM vs. control (SoC)
|
Composite of total HF hospitalisations and CV deaths up to 52 weeks after randomisation for FCM vs. placebo:
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Key secondary endpoint results |
Significant improvement (p < 0.001) with FCM vs. placebo in:
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Significant improvements in PGA, NYHA class and 6 MWT with FCM vs. placebo:
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Significant improvements in NYHA class and PGA with FCM vs. control:
Note: effect of FCM vs. control on NYHA class and PGA without imputation (observed values) were similar |
Total CV hospitalisations and CV deaths with FCM vs. placebo
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Safety endpoint results |
FCM vs. placebo (incidence per 100 patient-years at risk)
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FCM vs. placebo (incidence per 100 patient-years at risk)
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FCM vs. control (SoC)
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FCM vs. placebo
|
6 MWT, 6-min walk test; AFFIRM-AHF, Study to Compare Ferric Carboxymaltose With Placebo in Patients With Acute Heart Failure and Iron Deficiency; BNP, brain natriuretic peptide; CONFIRM-HF, Ferric CarboxymaltOse evaluatioN on perFormance in patients with IRon deficiency in coMbination with chronic Heart Failure; CI, confidence interval; CV, cardiovascular; EFFECT-HF, Effect of Ferric Carboxymaltose on Exercise Capacity in Patients With Iron Deficiency and Chronic Heart Failure; EQ-5D, EuroQol-5 Dimension; FAIR-HF, Ferinject assessment in patients with IRon deficiency and chronic Heart Failure; FCM, ferric carboxymaltose; Hb, haemoglobin; HF, heart failure; HFrEF, heart failure with reduced ejection fraction; HR, hazard ratio; ID, iron deficiency; IV, intravenous; KCCQ, Kansas City Cardiomyopathy Questionnaire; LS, least squares; LVEF, left ventricular ejection fraction; NA, not available; NT-proBNP, N-terminal pro B-type natriuretic peptide; NYHA, New York Heart Association; PGA, patient global assessment; Q4W, every four weeks; OR, odds ratio; QoL, quality of life; RR, rate ratio; SE, standard error; SoC, standard of care; TSAT, transferrin saturation.
This entry is adapted from the peer-reviewed paper 10.3390/jcm11112976