How to manage anemia in heart failure (HF)?

Management of Anemia in Heart Failure

Intravenous iron supplementation is strongly 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 hospitalizations. 1, 2

Diagnosis and Prevalence

• Iron deficiency is common in heart failure, affecting approximately 40-70% of patients, and can occur with or without anemia 2
• Iron deficiency is independently associated with heart failure disease severity, reduced exercise capacity, worse symptoms, and poorer prognosis 2
• Routine detection and management of iron deficiency and anemia in patients with heart failure remains an unmet medical need 1

Assessment of Anemia and Iron Deficiency

• Evaluate all patients with heart failure for anemia and iron deficiency as part of routine laboratory assessment 1, 2
• Define iron deficiency as ferritin <100 ng/mL or ferritin 100-300 ng/mL with transferrin saturation <20% 1, 2
• Before initiating iron therapy, screen for potentially treatable causes of iron deficiency (e.g., gastrointestinal bleeding) 2
• Additional laboratory tests should include serum creatinine, estimated GFR, vitamin B12, folic acid, and thyroid stimulating hormone 3

Treatment Recommendations

Intravenous Iron Therapy

• For patients with NYHA class II and III heart failure with reduced ejection fraction (HFrEF) and iron deficiency, intravenous iron replacement is recommended to improve functional status and quality of life 1, 2
• Ferric carboxymaltose (Injectafer) is FDA-approved for iron deficiency in adult patients with heart failure and NYHA class II/III to improve exercise capacity 4
• Dosing for ferric carboxymaltose in heart failure varies by weight and hemoglobin level:
  • For patients weighing <70 kg with Hb 10-14 g/dL: 1,000 mg on day 1 4
  • For patients weighing ≥70 kg with Hb 10-14 g/dL: 1,000 mg on day 1 and 500 mg at week 6 4
  • 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% 4

Erythropoietin-Stimulating Agents

• Erythropoietin-stimulating agents should NOT be used to improve morbidity and mortality in patients with heart failure and anemia 1
• The RED-HF trial showed that darbepoetin alfa did not result in benefit and was associated with a significant increase in thromboembolic events 1

Oral Iron Therapy

• There is an uncertain evidence base for oral iron repletion in heart failure-associated anemia 1
• Poor absorption and gastrointestinal side effects often lead to patient noncompliance with oral iron supplements 1

Evidence Supporting IV Iron Therapy

• The FAIR-HF trial demonstrated improvements in NYHA class and functional capacity with ferric carboxymaltose in iron-deficient heart failure patients 1, 2
• The CONFIRM-HF trial showed significant improvements in 6-minute walk test distance, NYHA class, Patient Global Assessment, quality of life, and fatigue scores with ferric carboxymaltose treatment 1, 4
• The FERRIC-HF study found that intravenous iron sucrose improved exercise capacity and symptoms in patients with heart failure, with more pronounced benefits in anemic patients 1
• A meta-analysis of 5 prospective controlled studies showed that IV iron therapy resulted in improved functional capacity and LVEF, but no significant reduction in mortality 1, 2

Important Considerations and Limitations

• The safety of IV iron is unknown in patients with heart failure and hemoglobin >15 g/dL 2
• The effect of treating iron deficiency in heart failure with preserved ejection fraction (HFpEF) remains unknown 2
• The long-term safety of iron therapy in heart failure is not fully established 2
• Hypersensitivity reactions, including anaphylactic-type reactions, have been reported with IV iron administration 4
• Monitor patients for signs and symptoms of hypersensitivity during and after IV iron administration for at least 30 minutes 4

Treatment Algorithm

1. Screen all heart failure patients for iron deficiency (ferritin <100 ng/mL or 100-300 ng/mL with TSAT <20%) 1, 2
2. Evaluate for underlying causes of iron deficiency 2, 3
3. For patients with NYHA class II-III HFrEF and iron deficiency:
   • Administer IV ferric carboxymaltose according to weight-based dosing 4
   • Monitor for improvement in functional capacity and symptoms 1, 4
   • Consider maintenance dosing based on follow-up iron studies 4
4. Do NOT use erythropoietin-stimulating agents for anemia management 1