title: Beneficial effects of long-term intravenous iron therapy with ferric carboxymaltose in patients with symptomatic heart failure and iron deficiency†.
abstract: OBJECTIVE
  The aim of this study was to evaluate the benefits and safety of long-term i.v. iron therapy in iron-deficient patients with heart failure (HF).
  
  
  RESULTS
  CONFIRM-HF was a multi-centre, double-blind, placebo-controlled trial that enrolled 304 ambulatory symptomatic HF patients with left ventricular ejection fraction ≤45%, elevated natriuretic peptides, and iron deficiency (ferritin <100 ng/mL or 100-300 ng/mL if transferrin saturation <20%). Patients were randomized 1 : 1 to treatment with i.v. iron, as ferric carboxymaltose (FCM, n = 152) or placebo (saline, n = 152) for 52 weeks. The primary end-point was the change in 6-min-walk-test (6MWT) distance from baseline to Week 24. Secondary end-points included changes in New York Heart Association (NYHA) class, Patient Global Assessment (PGA), 6MWT distance, health-related quality of life (QoL), Fatigue Score at Weeks 6, 12, 24, 36, and 52 and the effect of FCM on the rate of hospitalization for worsening HF. Treatment with FCM significantly prolonged 6MWT distance at Week 24 (difference FCM vs. placebo: 33 ± 11 m, P = 0.002). The treatment effect of FCM was consistent in all subgroups and was sustained to Week 52 (difference FCM vs. placebo: 36 ± 11 m, P < 0.001). Throughout the study, an improvement in NYHA class, PGA, QoL, and Fatigue Score in patients treated with FCM was detected with statistical significance observed from Week 24 onwards. Treatment with FCM was associated with a significant reduction in the risk of hospitalizations for worsening HF [hazard ratio (95% confidence interval): 0.39 (0.19-0.82), P = 0.009]. The number of deaths (FCM: 12, placebo: 14 deaths) and the incidence of adverse events were comparable between both groups.
  
  
  CONCLUSIONS
  Treatment of symptomatic, iron-deficient HF patients with FCM over a 1-year period resulted in sustainable improvement in functional capacity, symptoms, and QoL and may be associated with risk reduction of hospitalization for worsening HF (ClinicalTrials.gov number NCT01453608).
authors.affiliation: Department of Heart Diseases, Medical University, Wroclaw, Poland Department of Cardiology, Center for Heart Diseases, Clinical Military Hospital, Weigla 5 53-114, Wroclaw, Poland piotrponikowski@4wsk.pl.
authors.forename: Piotr
authors.initials: P
authors.lastname: Ponikowski
authors.affiliation: Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Dirk J
authors.initials: DJ
authors.lastname: van Veldhuisen
authors.affiliation: Heart Diseases Biomedical Research Group, IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain.
authors.forename: Josep
authors.initials: J
authors.lastname: Comin-Colet
authors.affiliation: Department of Internal Medicine I, University Hospital Würzburg, Würzburg, Germany Comprehensive Heart Failure Center, University of Würzburg, Würzburg, Germany.
authors.forename: Georg
authors.initials: G
authors.lastname: Ertl
authors.affiliation: CHU Pitié-Salpêtrière, Institut de Cardiologie, Paris, France.
authors.forename: Michel
authors.initials: M
authors.lastname: Komajda
authors.affiliation: Lomonosov Moscow State University, Moscow, Russia.
authors.forename: Viacheslav
authors.initials: V
authors.lastname: Mareev
authors.affiliation: Department of Cardiology, King's College Hospital, Denmark Hill, London SE5 9RS, UK.
authors.forename: Theresa
authors.initials: T
authors.lastname: McDonagh
authors.affiliation: Ukranian Strazhesko Institute of Cardiology, 5, Narodnoko Opolchenia St, Kiev 03151, Ukraine.
authors.forename: Alexander
authors.initials: A
authors.lastname: Parkhomenko
authors.affiliation: Maria Cecilia Hospital, GVM Care&Research-E.S. Health Science Foundation, Cotignola, Italy.
authors.forename: Luigi
authors.initials: L
authors.lastname: Tavazzi
authors.affiliation: Vifor Pharma, Glattbrugg, Switzerland.
authors.forename: Victoria
authors.initials: V
authors.lastname: Levesque
authors.affiliation: Vifor Pharma, Glattbrugg, Switzerland.
authors.forename: Claudio
authors.initials: C
authors.lastname: Mori
authors.affiliation: Vifor Pharma, Glattbrugg, Switzerland.
authors.forename: Bernard
authors.initials: B
authors.lastname: Roubert
authors.affiliation: Athens University Hospital Attikon, Athens, Greece.
authors.forename: Gerasimos
authors.initials: G
authors.lastname: Filippatos
authors.affiliation: Department of Cardiology, University Hospital Zurich, Switzerland.
authors.forename: Frank
authors.initials: F
authors.lastname: Ruschitzka
authors.affiliation: Department of Innovative Clinical Trials, University Medical Centre Göttingen, Göttingen, Germany.
authors.forename: Stefan D
authors.initials: SD
authors.lastname: Anker
mesh_terms: D000368:Aged; D002316:Cardiotonic Agents / Q000008:administration & dosage*; D004311:Double-Blind Method; D005260:Female; D005290:Ferric Compounds / Q000008:administration & dosage*; D006333:Heart Failure / Q000188:drug therapy*; D006760:Hospitalization / Q000706:statistics & numerical data; D006801:Humans; D007275:Injections, Intravenous; D000090463:Iron Deficiencies; D008134:Long-Term Care; D008297:Male; D008320:Maltose / Q000008:administration & dosage / Q000031:analogs & derivatives*; D011788:Quality of Life; D016896:Treatment Outcome
chemical_list: D002316:Cardiotonic Agents; D005290:Ferric Compounds; C522335:ferric carboxymaltose; D008320:Maltose
keywords: Ferric carboxymaltose; Heart failure; Iron deficiency