Biomarkers Used in the FAIR-HF Trial
The FAIR-HF trial used serum ferritin and transferrin saturation (TSAT) as the primary biomarkers to define iron deficiency in patients with chronic heart failure. 1, 2
Iron Deficiency Diagnostic Criteria
The trial defined iron deficiency using a two-tiered approach based on ferritin levels:
- Ferritin <100 ng/mL (regardless of transferrin saturation), OR
- Ferritin 100-300 ng/mL when transferrin saturation was <20% 1, 3, 2
Additional Baseline Biomarkers Assessed
Hematologic Parameters
- Hemoglobin levels: Patients were required to have hemoglobin between 9.5-13.5 g/dL (95-135 g/L) at enrollment 3, 2
- The trial specifically included both anemic and non-anemic patients to assess iron deficiency effects independent of anemia 2
Cardiac Function Markers
- NT-proBNP (N-terminal pro-B-type natriuretic peptide): Used as a surrogate endpoint to assess treatment effects on cardiac stress 1
- Left ventricular ejection fraction (LVEF): Required to be ≤40% for NYHA class II patients or ≤45% for NYHA class III patients 3, 2
Outcome Biomarkers Monitored
The trial tracked changes in several biomarkers during treatment:
- Serum ferritin: Monitored to assess iron repletion during correction and maintenance phases 1
- Transferrin saturation: Tracked to evaluate iron availability for erythropoiesis 1
- Hemoglobin: Measured to assess changes in anemia status, though improvements were seen regardless of baseline anemia 2
- NT-proBNP: Evaluated as a surrogate marker for cardiac function improvement 1
Clinical Context
The FAIR-HF trial demonstrated that these biomarkers successfully identified iron-deficient patients who would benefit from intravenous ferric carboxymaltose, with 50% of treated patients reporting being "much or moderately improved" compared to 28% receiving placebo 2. The trial showed improvements in NYHA functional class and quality of life at 24 weeks, with benefits observed in both anemic and non-anemic iron-deficient patients 1, 2.
Important caveat: While ferritin <100 ng/mL was the most commonly met criterion in iron deficiency trials, more recent evidence suggests that transferrin saturation and serum iron levels may be more strongly associated with functional capacity, hemoglobin levels, and clinical outcomes than ferritin alone 4.