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

Darlington O. Okonko,  Agnieszka Grzeslo,  Tomasz Witkowski,
Amit K. J. Mandal,  Robert M. Slater,  Michael Roughton,
Gabor Foldes, Thomas Thum,  Jacek Majda,
Waldemar Banasiak,  Constantinos G. Missouris,
Philip A. Poole-Wilson, Stefan D. Anker, Piotr Ponikowski,

Journal of the American College of Cardiology Vol. 51: No. 2, 2008

Objectives. 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.