Efficacy of ferric carboxymaltose in heart failure with iron deficiency: an individual patient data meta-analysis

Background and Aims Whereas a beneficial effect of intravenous ferric carboxymaltose (FCM) on symptoms and exercise capacity among patients with iron deficiency and heart failure (HF) has been consistently demonstrated, the effects of treatment on clinical events remain the subject of research. This meta-analysis aimed to characterize the effects of FCM therapy on hospitalizations and mortality.Methods Patient-level data from randomized, placebo-controlled FCM trials including adults with HF and iron deficiency with >= 52 weeks follow-up were analysed. The co-primary efficacy endpoints were (i) composite of total/recurrent cardiovascular hospitalizations and cardiovascular death and (ii) composite of total HF hospitalizations and cardiovascular death, through 52 weeks. Key secondary endpoints included individual composite endpoint components. Event rates were analysed using a negative binomial model. Treatment-emergent adverse events were also examined.Results Three FCM trials with a total of 4501 patients were included. Ferric carboxymaltose was associated with a significantly reduced risk of co-primary endpoint 1 (rate ratio 0.86; 95% confidence interval 0.75-0.98; P = .029; Cochran Q: 0.008), with a trend towards a reduction of co-primary endpoint 2 (rate ratio 0.87; 95% confidence interval 0.75-1.01; P = .076; Cochran Q: 0.024). Treatment effects appeared to result from reduced hospitalization rates, not improved survival. Treatment appeared to have a good safety profile and was well tolerated.Conclusions In iron-deficient patients with HF with reduced left ventricular ejection fraction, intravenous FCM was associated with significantly reduced risk of hospital admissions for HF and cardiovascular causes, with no apparent effect on mortality. Structured Graphical Abstract aData are full analysis set. bRate ratios and P-values are estimated using a negative binomial model on the number of events, including (fixed covariate) treatment, region, haemoglobin level at baseline, and (random covariate) study. CI, confidence interval; CV, cardiovascular; FCM, ferric carboxymaltose; HF, heart failure; HR, hazard ratio; PBO, placebo, RR, rate ratio; TSAT, transferrin saturation.