The IRONOUT-HF trial previously demonstrated that oral iron supplementation minimally increased iron stores and did not improve exercise capacity in patients with heart failure with a reduced ejection fraction (HFrEF) and iron deficiency.
The IRONOUT-HF trial was a double-blind, placebo-controlled, randomized clinical trial designed to test the efficacy and safety of oral iron polysaccharide compared to matching placebo among patients with HFrEF and iron deficiency. Study participants received oral iron polysaccharide 150 mg twice daily or matching placebo for 16 weeks. Response to oral iron was defined as a ferritin level >300 ng/mL or a ferritin level 100-300 ng/mL with a transferrin saturation >20% at the end of the study.
The final analytical cohort included 98 patients with HFrEF and iron deficiency at baseline. Study participants had a median (25th, 75th) age of 63 years (54 years, 71 years), included 40% women (N = 39). After 16 weeks of therapy, 24 patients (24%) responded to oral iron supplementation while 74 patients (76%) remained iron deficient despite treatment. There was no association between response to oral iron supplementation and improvement in functional status (i.e. peak VO2 or anaerobic threshold), myocardial stress (i.e. NT-proBNP levels), or HRQOL (i.e. Kansas City Cardiomyopathy Questionnaire) at week 16.
This study failed to identify a subset of responders more likely to derive a clinical benefit from oral iron therapy and does not support its routine use in patients with symptomatic HFrEF and iron deficiency.
aDivision of Cardiology, The Permanente Medical Group, San Francisco
bDivision of Research, Kaiser Permanente Northern California, Oakland, California
cDivision of Cardiology, Massachusetts General Hospital, Boston, Massachusetts
dDivision of Cardiology, Duke University Medical Center, Durham
eDuke Clinical Research Institute, Durham, North Carolina
fDepartment of Medicine, University of Mississippi Medical Center, Jackson, Mississippi
gDivision of Cardiology, Stanford Hospital and Clinics, Palo Alto, California, USA
Correspondence to Andrew P. Ambrosy, MD, Division of Cardiology, The Permanente Medical Group, 2238 Geary Boulevard, 8th Floor, San Francisco, CA 94114, USA E-mail: firstname.lastname@example.org
Received 13 August, 2018
Accepted 24 October, 2018