Effect of Ferric Carboxymaltose on Exercise Capacity in Patients with Chronic Heart Failure and Iron Deficiency
Background—Iron deficiency is common in patients with heart failure (HF), and is associated with reduced exercise capacity and poor outcomes. Whether correction of iron deficiency with (intravenous) ferric carboxymaltose (FCM) affects peak oxygen consumption [peak VO2], an objective measure of exercise intolerance in HF, has not been examined.
Methods—We studied patients with systolic HF (left ventricular ejection fraction [LVEF] ≤45%) and mild to moderate symptoms despite optimal HF medication, Patients were randomized 1:1 to treatment with FCM for 24 weeks or standard of care. The primary endpoint was the change in peak VO2 from baseline to 24 weeks. Secondary endpoints included effect hematinic and cardiac biomarkers, quality of life, and safety. For the primary analysis, patients who died had a value of zero imputed for 24-week peak VO2. Additional sensitivity analyses were performed to determine the impact of imputation of missing peak VO2 data.
Results—A total of 172 HF patients were studied are received FCM (n=86) or standard of care (control group, n=86). At baseline, the groups were well-matched; mean age was 64 years, 75% were male, LVEF was 32%, peak VO2 13.5 mL/min/kg. FCM significantly increased serum ferritin and transferrin saturation. At 24 weeks, peak VO2 had decreased in the control group (least square means -1.19±0.389 mL/min/kg), but was maintained on FCM (-0.16±0.387 mL/min/kg; p=0.020 between groups). In a sensitivity analysis, in which missing data were not imputed, peak VO2 at 24 weeks decreased by 0.63±0.375 mL/min/kg in the control group, and by 0.16±0.373 mL/min/kg in the FCM group; p=0.23 between groups). Patients' global assessment and functional class as assessed by New York Heart Association improved on FCM vs. standard of care.
Conclusions—Treatment with intravenous FCM in patients with HF and iron deficiency improve iron stores. Although a favourable effect on peak VO2 was observed on FCM, compared to standard of care in the primary analysis, this effect was highly sensitive to the imputation strategy for peak VO2 among patients who died. Whether FCM is associated with an improved outcome in these high-risk patients needs further study.
Clinical Trial Registration—URL: https://clinicaltrials.gov Unique identifier: NCT01394562.
- Received January 20, 2017.
- Revision received June 17, 2017.
- Accepted June 30, 2017.