Intravenous Ferric Carboxymaltose in Ischemic Versus Non-Ischemic Heart Failure and Iron Deficiency: Insights From FAIR-HF2.

Background: Previous studies have suggested that patients with ischemic etiology of heart failure (HF) and iron deficiency may derive greater benefits with intravenous ferric carboxymaltose (FCM). We aim to assess the effects of FCM versus placebo in patients with ischemic versus non-ischemic etiology of HF.

Methods and results: The FAIR-HF2 trial included 1105 patients with HF, with a left-ventricular ejection fraction ≤45%, and concomitant iron deficiency. Patients were randomized 1:1 to either intravenous FCM or placebo. Ischemic etiology was defined as investigator reported or prior coronary revascularization or myocardial infarction. The primary endpoints were time-to-first event of cardiovascular death or HF hospitalization, total HF hospitalizations, and time-to-first event of cardiovascular death or HF hospitalization in patients with transferrin saturation <20% at baseline. Of 1105 patients, 858 (78%) had ischemic etiology of HF. These were more frequently older, men and had more co-morbidities. For the first primary endpoint, FCM was associated with a hazard ratio (HR) of 0.85 (95%CI: 0.66-1.10, p=0.23) for ischemic HF and 0.61 (95% CI: 0.39-0.98, p=0.038) for non-ischemic HF (P-interaction=0.26). The HR for the second primary endpoint was 0.87 (95% CI: 0.63-1.21, p=0.41) for ischemic HF and 0.57 (95% CI: 0.35-0.94, p=0.028) for non-ischemic HF (P-interaction=0.17), while HR for the third primary endpoint was 0.84 (95% CI: 0.62-1.14, p=0.27) for ischemic HF and 0.63 (95% CI: 0.37-1.07, p=0.087) for non-ischemic HF (P-interaction=0.35).

Conclusions: Effect of intravenous iron supplementation is likely similar in patients with ischemic or non-ischemic etiology of HF, just like other HF guideline-directed medical therapies.