The Effect of Intravenous Ferric Carboxymaltose on Red Cell Distribution Width: A Subanalysis of the FAIR-HF Study

AIMS: Red cell distribution width (RDW), a measure of variability in red blood cell size, is a novel prognostic marker in chronic heart failure (CHF). Iron deficiency contributes to elevated RDW. In the FAIR-HF trial, i.v. ferric carboxymaltose (FCM) improved the 6 min walk test (6MWT) distance in iron-deficient CHF patients. We studied the effect of FCM on RDW and the relationship between RDW and 6MWT distance. METHODS AND RESULTS: In FAIR-HF, iron-deficient CHF patients were randomized to FCM or placebo in a 2:1 ratio. From the total cohort (n = 459), we included 415 patients in whom RDW values and 6MWT distance were available for baseline and at least one follow-up visit (after 4, 12, and 24 weeks). Baseline RDW was higher in anaemic (haemoglobin <12 g/dL) compared with non-anaemic patients [15.2% (14.0-16.8) vs. 14.2% (13.4-15.4), P < 0.0001, median (interquartile range)]. In multivariate analysis, RDW was significantly associated with transferrin saturation (P < 0.001) and C-reactive protein levels (P = 0.002). Treatment with FCM led to a biphasic response; RDW increased within 4 weeks (+0.54% absolute change from baseline, P = 0.01) but fell to values below the placebo group after 24 weeks (-1.0 %, P = 0.03). The 6MWT distance and RDW were inversely related at baseline (r = -0.30, P < 0.0001). In all patients, the increase in 6MWT distance after 24 weeks was significantly correlated with a decrease in RDW (r= -0.25, P < 0.0001), even after adjustment for changes in haemoglobin. CONCLUSIONS: Iron deficiency in CHF is associated with high RDW, even after adjustment for the presence of anaemia. Treatment with i.v. FCM in iron-deficient CHF patients decreases RDW.