Effect of intravenous iron sucrose on exercise tolerance in anemic and nonanemic patients with symptomatic chronic heart failure and iron deficiency FERRIC-HF: a randomized, controlled, observer-blinded trial.
OBJECTIVE
We tested the hypothesis that intravenous iron improves exercise tolerance in anemic and nonanemic patients with symptomatic chronic heart failure (CHF) and iron deficiency.


BACKGROUND
Anemia is common in heart failure. Iron metabolism is disturbed, and administration of iron might improve both symptoms and exercise tolerance.


METHODS
We randomized 35 patients with CHF (age 64 +/- 13 years, peak oxygen consumption [pVO2] 14.0 +/- 2.7 ml/kg/min) to 16 weeks of intravenous iron (200 mg weekly until ferritin >500 ng/ml, 200 mg monthly thereafter) or no treatment in a 2:1 ratio. Ferritin was required to be <100 ng/ml or ferritin 100 to 300 ng/ml with transferrin saturation <20%. Patients were stratified according to hemoglobin levels (<12.5 g/dl [anemic group] vs. 12.5 to 14.5 g/dl [nonanemic group]). The observer-blinded primary end point was the change in absolute pVO2.


RESULTS
The difference (95% confidence interval [CI]) in the mean changes from baseline to end of study between the iron and control groups was 273 (151 to 396) ng/ml for ferritin (p < 0.0001), 0.1 (-0.8 to 0.9) g/dl for hemoglobin (p = 0.9), 96 (-12 to 205) ml/min for absolute pVO2 (p = 0.08), 2.2 (0.5 to 4.0) ml/kg/min for pVO2/kg (p = 0.01), 60 (-6 to 126) s for treadmill exercise duration (p = 0.08), -0.6 (-0.9 to -0.2) for New York Heart Association (NYHA) functional class (p = 0.007), and 1.7 (0.7 to 2.6) for patient global assessment (p = 0.002). In anemic patients (n = 18), the difference (95% CI) was 204 (31 to 378) ml/min for absolute pVO2 (p = 0.02), and 3.9 (1.1 to 6.8) ml/kg/min for pVO2/kg (p = 0.01). In nonanemic patients, NYHA functional class improved (p = 0.06). Adverse events were similar.


CONCLUSIONS
Intravenous iron loading improved exercise capacity and symptoms in patients with CHF and evidence of abnormal iron metabolism. Benefits were more evident in anemic patients. (Effect of Intravenous Ferrous Sucrose on Exercise Capacity in Chronic Heart Failure; http://www.clinicaltrials.gov/ct/show/NCT00125996; NCT00125996).
Okonko
Darlington O
DO
Clinical Cardiology, NHLI, Imperial College London, London, United Kingdom. d.okonko@imperial.ac.uk
Grzeslo
Agnieszka
A
Witkowski
Tomasz
T
Mandal
Amit K J
AK
Slater
Robert M
RM
Roughton
Michael
M
Foldes
Gabor
G
Thum
Thomas
T
Majda
Jacek
J
Banasiak
Waldemar
W
Missouris
Constantinos G
CG
Poole-Wilson
Philip A
PA
Anker
Stefan D
SD
Ponikowski
Piotr
P
D000368:Aged; D000704:Analysis of Variance; D018798:Anemia, Iron-Deficiency / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality; D002908:Chronic Disease; D016001:Confidence Intervals; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D017079:Exercise Tolerance / Q000187:drug effects*; D005260:Female; D005290:Ferric Compounds / Q000008:administration & dosage*; D005500:Follow-Up Studies; D006333:Heart Failure / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D010101:Oxygen Consumption / Q000187:drug effects* / Q000502:physiology; D011336:Probability; D011446:Prospective Studies; D012016:Reference Values; D018570:Risk Assessment; D015996:Survival Rate; D016896:Treatment Outcome
D005290:Ferric Compounds