Effects of ferric citrate hydrate in patients with chronic kidney disease and heart failure: subgroup analysis of a long-term, real-world, post-marketing surveillance study

Background Iron deficiency is widely present in patients with heart failure (HF) and is associated with an increased risk of mortality and poor clinical outcomes regardless of anemia. HF is highly prevalent in patients with chronic kidney disease (CKD). However, existing oral iron preparations have failed to improve iron-related parameters in patients with HF, and intravenous iron preparations are recommended. Ferric citrate hydrate (FC) is an oral iron-based phosphate binder for CKD that is also approved for the treatment of patients with iron-deficiency anemia in Japan. In this subgroup analysis, we evaluated the effect of oral FC on iron-related parameters in CKD patients with and without HF. Methods We examined iron- and phosphate-related parameters and adverse drug reactions in subpopulations of CKD patients with and without HF enrolled in a previously reported 104-week, real-world, post-marketing surveillance study of FC in Japan. Results Among 2811 enrolled CKD patients, 348 patients had HF and 2352 did not have HF, including 166 and 1401 undergoing hemodialysis (HD), 36 and 173 undergoing peritoneal dialysis (PD), and 146 and 778 non-dialysis-dependent (ND) patients, respectively. The mean changes (95% confidence interval (CI)) in serum ferritin from baseline to week 36 were 90.98 (62.99–118.97) and 81.86 (72.68–91.03) ng/mL in HD, 158.64 (108.91–208.36) and 132.91 (98.59–167.23) ng/mL in PD, and 68.06 (40.40–95.73) and 99.75 (81.10–118.40) ng/mL in ND group, respectively. The mean changes (95% CI) in transferrin saturation (TSAT) (%) from baseline to week 12 in patients with and without HF were 12.79 (9.15–16.44) % and 9.57 (8.46–10.68) % in HD, 9.55 (1.31–17.78) % and 4.96 (1.44–8.48) % in PD, and 5.85 (2.02–9.69) % and 5.21 (3.34–7.09) in ND patients, respectively. Levels of these parameters were well maintained thereafter. Mean serum phosphate levels decreased after FC treatment initiation and were well maintained in all groups. Conclusions This study demonstrated that oral FC had a tendency to increase serum ferritin and TSAT, and controlled serum phosphate in CKD patients regardless of the presence of HF. Trial registration This surveillance was conducted in accordance with the Good Post-marketing Study Practice of Ministry of Health, Labour, and Welfare in Japan.