From Department of Cardiology, University Medical Center Groningen, University of Groningen, The Netherlands (D.J.v.V., P.v.d.M., A.A.V.); Department of Heart Diseases, Medical University, Clinical Military Hospital, Wroclaw, Poland (P.P.); Department of Cardiology, University Hospital, Brescia, Italy (M.M.); Universitätsklinikum des Saarlandes, Homburg/Saar, Germany (M.B.); I.M. Sechenov First Moscow State Medical University, Moscow, Russia (A.D.); King’s College Hospital, London, United Kingdom (I.C.M.); Division of Cardiology and Metabolism, Department of Cardiology (CVK) and Berlin-Brandenburg Center for Regenerative Therapies (S.D.A.); Deutsches Zentrum für Herz-Kreislauf-Forschung, Berlin (S.D.A.); Charité Universitätsmedizin Berlin, Germany (S.D.A.); Department of Cardiology and Pneumology, University Medicine Göttingen, Germany (S.D.A.); Vifor Pharma, Glattbrugg, Switzerland (B.R., L.Z.); and Hopital Lariboisiere, University Paris Diderot, UMR-S942, France (A.C.-S.).
Checking for direct PDF access through Ovid
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 ≤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 end point was the change in peak VO2 from baseline to 24 weeks. Secondary end points included the effect on hematinic and cardiac biomarkers, quality of life, and safety. For the primary analysis, patients who died had a value of 0 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 patients with HF were studied and 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, mean left ventricular ejection fraction was 32%, and peak VO2 was 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 the New York Heart Association improved on FCM versus standard of care.Conclusions:Treatment with intravenous FCM in patients with HF and iron deficiency improves iron stores. Although a favorable effect on peak VO2 was observed on FCM, compared with 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: http://www.clinicaltrials.gov. Unique identifier: NCT01394562.