Author + information
- Received November 9, 2006
- Revision received August 14, 2007
- Accepted September 11, 2007
- Published online January 15, 2008.
- Darlington O. Okonko, BSc, MRCP⁎,2,3,4,5,⁎ (, )
- Agnieszka Grzeslo, MD†,4,
- Tomasz Witkowski, MD†,
- Amit K.J. Mandal, MRCP‡,
- Robert M. Slater, MBBS‡,
- Michael Roughton, MSc⁎,
- Gabor Foldes, MD, PhD⁎,
- Thomas Thum, MD⁎,§,
- Jacek Majda, MD†,
- Waldemar Banasiak, MD, PhD†,
- Constantinos G. Missouris, MD‡,
- Philip A. Poole-Wilson, MD, FMedSci⁎,2,5,7,
- Stefan D. Anker, MD, PhD⁎∥,1,2,6 and
- Piotr Ponikowski, MD, PhD†,1,2,6
- ↵⁎Reprint requests and correspondence:
Dr. Darlington O. Okonko, Clinical Cardiology, NHLI, Dovehouse Street, London SW3 6LY, United Kingdom.
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. (Effect of Intravenous Ferrous Sucrose on Exercise Capacity in Chronic Heart Failure; http://www.clinicaltrials.gov/ct/show/NCT00125996; NCT00125996)
↵1 Drs. Ponikowski and Anker contributed equally to this article.
↵2 Drs. Okonko, Anker, Poole-Wilson, and Ponikowski designed and/or oversaw the study.
↵3 Dr. Okonko drafted the study protocol, case report forms and manuscript.
↵4 Drs. Okonko and Grzeslo monitored the trial.
↵5 Drs. Poole-Wilson and Okonko are supported by the British Heart Foundation, London, United Kingdom (FS/03/104/16341).
↵6 Drs. Ponikowski and Anker are consultants to Vifor International and have spoken at symposia.
↵7 Dr. Poole-Wilson has attended Vifor advisory meetings.
All authors were involved in data acquisition, data analysis, and review of the manuscript. Intravenous iron was supplied by Vifor International (St. Galen, Switzerland). An unrestricted grant was provided by Vifor International to Imperial College London.
- Received November 9, 2006.
- Revision received August 14, 2007.
- Accepted September 11, 2007.
- American College of Cardiology Foundation