Amsterdam, Netherlands – 26 Aug 2023: In iron-deficient patients with heart failure and reduced or mildly reduced left ventricular ejection fraction, intravenous ferric carboxymaltose (FCM) is associated with a reduced risk of the composite outcome of total cardiovascular hospitalisation and cardiovascular death through 52 weeks compared with placebo, according to late breaking research presented in a Hot Line session today at ESC Congress 2023.1
Iron deficiency is common in heart failure, with a prevalence of 30–80%, and is associated with increased mortality and hospitalisation.2 Randomised controlled trials of intravenous iron in iron-deficient patients with heart failure have shown improvements in symptoms, functional capacity and quality of life, but the effect on clinical events has been unclear.3.4 The current meta-analysis evaluated the effects of FCM therapy on hospitalisations and mortality in iron-deficient patients with heart failure and reduced or mildly reduced left ventricular ejection fraction.
The meta-analysis pooled individual participant data from three randomised, placebo-controlled trials of FCM in adult patients with heart failure and iron deficiency with at least 52 weeks of follow up: CONFIRM-HF, AFFIRM-AHF and HEART-FID. There were two primary efficacy endpoints: 1) composite of total cardiovascular hospitalisations and cardiovascular death and 2) composite of total heart failure hospitalisations and cardiovascular death. Both endpoints were examined through 52 weeks of follow up. Key secondary endpoints included individual components of the composite endpoints.
In the three trials, a total of 4,501 patients with heart failure and reduced or mildly reduced left ventricular ejection fraction and iron deficiency were randomly assigned to FCM (n=2,251) or placebo (n=2,250). The mean age of the total population was 69 years, 63% were men, and the mean left ventricular ejection fraction was 32%.
FCM therapy significantly reduced the co-primary composite endpoint of total cardiovascular hospitalisations and cardiovascular death compared with placebo, with a rate ratio (RR) of 0.86 (95% confidence interval [CI] 0.75 to 0.98; p=0.029). There was a trend towards reduction of the co-primary composite endpoint of total heart failure hospitalisations and cardiovascular death but it failed to reach statistical significance (RR 0.87; 95% CI 0.75 to 1.01; p=0.076).
FCM therapy was associated with a 17% relative rate reduction in total cardiovascular hospitalisations (RR 0.83; 95% CI 0.73 to 0.96; p=0.009) and a 16% relative rate reduction in total heart failure hospitalisations (RR 0.84; 95% CI 0.71 to 0.98; p=0.025). There was no effect of FCM administration on mortality.
In subgroup analyses, patients in the lowest transferrin saturation (TSAT) tertile (<15%) derived greater benefit from FCM on the composite endpoint of total cardiovascular hospitalisations or cardiovascular death than those with higher baseline TSAT (interaction p=0.019).
Treatment with FCM appeared to be safe and well-tolerated.
Principal investigator Professor Piotr Ponikowski of Wroclaw Medical University, Poland said: “This was the largest and most up-to-date analysis of the effect of FCM in iron-deficient heart failure patients with reduced or mildly reduced ejection fraction. FCM was associated with a reduction in the composite endpoint of total cardiovascular hospitalisations and cardiovascular death compared with placebo, and with significantly reduced risks of hospitalisation due to heart failure or cardiovascular causes, with no effect on survival. The findings indicate that intravenous FCM should be considered in iron-deficient patients with heart failure and reduced or mildly reduced ejection fraction to reduce the risk of hospitalisation due to heart failure and cardiovascular causes.”