FAIR-HF Trial Efficacy Outcomes
The FAIR-HF trial demonstrated that 50% of patients treated with intravenous ferric carboxymaltose reported being much or moderately improved compared to 28% receiving placebo (odds ratio 2.51), with 47% achieving NYHA class I or II versus 30% in the placebo group (odds ratio 2.40) at 24 weeks. 1
Primary Endpoints
The trial evaluated two co-primary endpoints at week 24 in iron-deficient heart failure patients (ferritin <100 ng/mL or 100-300 ng/mL with transferrin saturation <20%):
Patient Global Assessment (PGA)
- 50% of ferric carboxymaltose patients reported being much or moderately improved versus 28% with placebo 2, 1
- Odds ratio for improvement: 2.51 (95% CI 1.75-3.61) 2, 1
NYHA Functional Class
- 47% of ferric carboxymaltose patients achieved NYHA class I or II at week 24 versus 30% with placebo 2, 1
- Odds ratio for improvement by one class: 2.40 (95% CI 1.55-3.71) 3, 2, 1
These improvements occurred equally in both anemic and non-anemic patients, demonstrating that iron deficiency itself—not just anemia—drives functional impairment in heart failure 4, 1.
Secondary Endpoints
Functional Capacity
- Significant improvements in 6-minute walk test distance were observed with ferric carboxymaltose treatment 3, 1
- The distance walked increased progressively at weeks 4,12, and 24 3
Quality of Life Measures
- Significant improvements in Kansas City Cardiomyopathy Questionnaire (KCCQ) overall scores were demonstrated 3, 2, 1
- EQ-5D Visual Analogue Scale scores improved significantly with treatment 3, 4
- Fatigue scores showed significant improvement in the ferric carboxymaltose group 3, 2
Consistency Across Subgroups
- Benefits were similar regardless of baseline anemia status (hemoglobin ≤120 g/L vs >120 g/L) 4
- Odds ratios for PGA improvement: 2.48 in anemic patients versus 2.60 in non-anemic patients (p=0.97 for interaction) 4
- Odds ratios for NYHA improvement: 1.90 in anemic patients versus 3.39 in non-anemic patients (p=0.51 for interaction) 4
Safety Profile
No differences in death rates or adverse events were observed between ferric carboxymaltose and placebo groups 3, 2, 1. The trial demonstrated an acceptable safety profile with similar rates of serious adverse events in both groups 1.
Critical Limitations
The FAIR-HF trial was not powered to detect differences in mortality or hospitalization endpoints, which represents the most important limitation 3, 2. The ACC/AHA guidelines explicitly note that "controlled trials have been underpowered to detect reductions in hard clinical endpoints" and that "a strong recommendation for intravenous iron repletion must await the results of an appropriately powered trial on morbidity and mortality" 3.
Subsequent Validation
The FAIR-HF findings were confirmed in the CONFIRM-HF trial (n=304), which demonstrated sustained improvements in 6-minute walk test distance at 24 weeks (treatment effect of 25 meters, p=0.007) 3, 2, 5. The CONFIRM-HF trial extended follow-up to 52 weeks and showed persistent benefits in NYHA class, patient global assessment, quality of life, and fatigue scores 3, 2.
More recent data from AFFIRM-AHF (2020) showed that ferric carboxymaltose reduced total heart failure hospitalizations (rate ratio 0.74, p=0.013) and the composite of first heart failure hospitalization or cardiovascular death (hazard ratio 0.80, p=0.030), though it had no effect on cardiovascular mortality 6.