The impact of intravenous ferric carboxymaltose on renal function: an analysis of the FAIR-HF study

Abstract

Aims: Anaemia and iron deficiency are constituents of the cardio-renal syndrome in chronic heart failure (CHF). We investigated the effects of i.v. iron in iron-deficient CHF patients on renal function, and the efficacy and safety of this therapy in patients with renal dysfunction.

Methods and results: The FAIR-HF trial randomized 459 CHF patients with iron deficiency (ferritin <100 µg/L, or between 100 and 299 µg/L if transferrin saturation was <20%): 304 to i.v. ferric carboxymaltose (FCM) and 155 to placebo, and followed-up for 24 weeks. Renal function was assessed at baseline and at weeks 4, 12, and 24, using the estimated glomerular filtration rate (eGFR, mL/min/1.73 m(2) ), calculated from the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula. At baseline, renal function was similar between groups (62.4 ± 20.6 vs. 62.9 ± 23.4 mL/min/1.73 m(2) , FCM vs. placebo). Compared with placebo, treatment with FCM was associated with an increase in eGFR [treatment effect: week 4, 2.11 ± 1.21 (P = 0.082); week 12, 2.41 ± 1.33 (P = 0.070); and week 24, 2.98 ± 1.44 mL/min/1.73 m(2) (P = 0.039)]. This effect was seen in all pre-specified subgroups (P > 0.20 for interactions). No interaction between the favourable effects of FCM and baseline renal function was seen for the primary endpoints [improvement in Patient Global Assessment (P = 0.43) and NYHA class (P = 0.37) at 24 weeks]. Safety and adverse event profiles were similar in patients with baseline eGFR <60 and ≥60 mL/min/1.73 m(2) .

Conclusions: Treatment of iron deficiency in CHF patients with i.v. FCM was associated with an improvement in renal function. FCM therapy was effective and safe in CHF patients with renal dysfunction.

Keywords: Chronic heart failure; Ferric carboxymaltose; Iron deficiency; Renal function.

Figure 1

Impact of i.v. ferric carboxymaltose (FCM) treatment on renal function vs. placebo. Values are expressed as least squares means ± SE. eGFR, estimated glomerular filtration rate.

Figure 2

Treatment effect on renal function in pre-defined subgroups at week 24. Treatment effect was expressed as a continuous variable, being the least squares means change from baseline ± 1 SE. BMI, body mass index; eGFR, estimated glomerular filtration rate; Hb, haemoglobin; HF, heart failure.

Figure 3

Impact of i.v. ferric carboxymaltose (FCM) on renal function categorized by change in estimated glomerular filtration rate (eGFR; mL/min/1.73 m²) at week 24. Data were available for 347 patients with a change in eGFR at week 24 (106 patients in the placebo group and 241 patients in the FCM group).

Figure 4

Primary (A) and secondary (B) endpoints of the FAIR-HF trials stratified by baseline estimated glomerular filtration rate (eGFR; mL/min/1.73 m²). FCM, ferric carboxymaltose.