What are the guidelines for iron supplementation in patients with heart failure and iron deficiency?

Iron Supplementation Guidelines for Heart Failure

Intravenous iron supplementation is recommended for patients with NYHA class II and III heart failure who have iron deficiency (ferritin <100 ng/mL or 100-300 ng/mL with transferrin saturation <20%) to improve functional status, quality of life, and reduce heart failure hospitalizations. 1, 2

Screening and Diagnosis of Iron Deficiency

• Iron deficiency is common in heart failure, affecting approximately 40-70% of patients, and can exist with or without anemia 2
• Iron status evaluation should be performed in all newly diagnosed heart failure patients (Class I recommendation) 1
• Iron status should also be evaluated in patients with existing chronic heart failure, particularly if they remain symptomatic despite optimal heart failure medications 1
• Re-evaluation of iron status should be considered 1-2 times per year and after hospitalization for heart failure 1
• Iron deficiency is defined as:
  • Ferritin <100 ng/mL (absolute iron deficiency) OR
  • Ferritin 100-300 ng/mL with transferrin saturation <20% (functional iron deficiency) 1
• Both ferritin and transferrin saturation should be measured simultaneously and evaluated together 1
• Mean corpuscular volume, mean corpuscular hemoglobin, and serum iron alone are unreliable markers for iron deficiency in heart failure patients 1

Treatment Recommendations

• For NYHA class II-III heart failure patients with iron deficiency:
  • Intravenous iron is recommended (Class IIb recommendation, Level of Evidence B-R) 1
  • Ferric carboxymaltose is the most studied IV iron formulation in heart failure trials 2, 3
  • Oral iron supplementation is not recommended due to poor absorption and inadequate repletion of iron stores in heart failure patients 1, 4

Dosing of Intravenous Iron

For ferric carboxymaltose (Injectafer) 5:

• For patients weighing <70 kg:
  • Hb <10 g/dL: 1,000 mg on day 1, followed by 500 mg at week 6
  • Hb 10-14 g/dL: 1,000 mg on day 1, no dose at week 6
  • Hb >14 to <15 g/dL: 500 mg on day 1, no dose at week 6
• For patients weighing ≥70 kg:
  • Hb <10 g/dL: 1,000 mg on day 1, followed by 1,000 mg at week 6
  • Hb 10-14 g/dL: 1,000 mg on day 1, followed by 500 mg at week 6
  • Hb >14 to <15 g/dL: 500 mg on day 1, no dose at week 6
• Maintenance dose of 500 mg at weeks 12,24, and 36 if ferritin <100 ng/mL or ferritin 100-300 ng/mL with transferrin saturation <20%

Clinical Evidence Supporting IV Iron

• FAIR-HF trial demonstrated significant improvements in NYHA class and functional capacity with ferric carboxymaltose in iron-deficient heart failure patients 1, 2
• CONFIRM-HF trial showed improvements in 6-minute walk test in a larger cohort of patients with iron deficiency and heart failure 1, 2
• Meta-analyses have shown that IV iron is associated with:
  • Improved functional capacity and left ventricular ejection fraction 1
  • Reduced hospitalization for heart failure 1, 4
  • No significant reduction in mortality has been consistently demonstrated 1, 4

Important Clinical Considerations

• Before initiating iron therapy, patients should be screened for potentially treatable causes of iron deficiency (e.g., gastrointestinal bleeding) 2
• Do not administer IV iron if hemoglobin >15 g/dL 1, 5
• The long-term safety of iron therapy in heart failure with preserved ejection fraction (HFpEF) is not well established 2
• Iron deficiency remains frequently under-diagnosed and under-treated in heart failure patients 1, 6
• Oral iron supplements may slightly increase serum iron levels but do not significantly improve transferrin saturation or exercise capacity in heart failure patients 7

Monitoring After Treatment

• Monitor serum phosphate levels in patients at risk for low serum phosphate who require repeat treatment 5
• Treat hypophosphatemia as medically indicated 5
• Consider repeating iron status evaluation if symptoms recur or at regular intervals (1-2 times per year) 1