Oral ferric maltol in heart failure patients with iron deficiency anaemia according to NYHA functional class

Background Iron deficiency, a frequent comorbidity in patients with heart failure (HF), is associated with impaired functional capacity, reduced quality of life (QoL), and worse prognosis. Current ESC guidelines recommend intravenous iron supplementation in patients with HF with reduced or mildly reduced ejection fraction (HFrEF and HFmrEF), whereas oral iron therapy has failed to demonstrate consistent clinical benefits. The multicentre, open-label, prospective ORION-HF trial with oral ferric maltol has proven to significantly increase hemoglobin in HF patients with iron deficiency anaemia at 16 weeks. This prespecified subanalysis evaluates whether treatment effects differ according to baseline NYHA functional class. Methods A total of 50 patients were enrolled in ORION-HF. 41 patients received at least one dose of ferric maltol and completed 16-week follow-up. Assessments included laboratory parameters, 6-minute walk distance test (6MWD), and patient-reported outcome measures using the Kansas City Cardiomyopathy Questionnaire (KCCQ). Patients were stratified into NYHA class II and NYHA class III–IV groups. Changes from baseline to week 16 were analyzed. Results The overall mean age was 80 years, 32% were female, and 39% had a left ventricular ejection fraction (LVEF) <50%. Guideline-directed heart failure therapy was well established across the study population. The NYHA class III–IV group (n=13) was smaller than the NYHA class II group (n=28). Patients with NYHA class III–IV were younger, had lower LVEF, and were more frequently treated with beta-blockers and mineralocorticoid receptor antagonists. No significant differences were observed between groups with respect to the remaining baseline characteristics (Table 1). Hemoglobin and transferrin saturation increased significantly in both NYHA class II and NYHA class III-IV groups (+1.38 vs. +2.13 g/dL; both p<0.001), as did transferrin saturation (Figure 1). KCCQ overall summary score, symptom frequency, and social limitation scores improved significantly in patients with NYHA class II, but not in those with NYHA class III-IV, whereas QoL scores improved significantly in both groups. 6MWD increased in both groups, with a trend toward greater absolute improvement observed among patients with NYHA class III-IV (71, 6 m vs 25.4 m, p for interaction =0.199). Conclusions Oral ferric maltol was associated with significant increase in hemoglobin and transferrin saturation across NYHA classes. Improvements in patient-reported outcomes were more pronounced in patients with milder symptoms, whereas greater gains in functional capacity were observed in more symptomatic patients. These findings suggest beneficial clinical effects of oral iron supplementation across the HF severity spectrum. Further larger-scale studies are needed to validate these findings.