トライアルの結果、経静脈的投与の鉄補充が支持されたが経口による鉄補充は支持されなかった(LBCT.04)

Therapeutic options to further improve functional capacity and symptoms among heart failure patients are limited. Iron deficiency is present in about half of heart failure patients with reduced ejection fraction and the usefulness of inexpensive, readily available oral iron supplementation in heart failure is unknown.

Previous studies suggest that iron deficiency with or without anemia further reduces this exercise capacity by 10 percent to up to 50 percent measured by peak oxygen consumption.  Treating iron deficiency with intravenous ferric carboxymaltose (FCM) and has been shown to reduce symptoms, improve quality of life and increase six-minute walking distance in this population.

The issue of iron supplementation in patients with chronic heart failure remains unsettled after two new studies testing oral and intravenous iron yielded conflicting results at the American Heart Association 2016 Scientific Sessions.

Peak oxygen uptake (VO₂) significantly improved when compared with standard of care after three intravenous injections of ferric carboxymaltose in HF patients with and without anemia in EFFECT-HF, while functional capacity and other outcomes failed to improve with a considerably cheaper oral iron supplement in the IRONOUT study.

In Oral Iron Repletion effects ON Oxygen UpTake in Heart Failure (IRONOUT HF) Trial researchers evaluated whether oral iron supplementation could improve exercise capacity in heart failure patients.  IRONOUT HF is a multi-center, randomized, double-blinded, placebo-controlled trial of oral iron polysaccharide (300 mg/day) compared to matching placebo. The trial enrolled 225 heart failure patients (average age 63, 36 percent female, 25 percent black) with reduced pumping ability and iron deficiency.

The primary endpoint is change in peak oxygen uptake (pkVO₂) measured at baseline and at 16 weeks. Secondary endpoints include assessments of the impact of oral iron on submaximal exercise capacity; plasma NT-pro BNP levels; and health status.

Gregory D. Lewis, Massachusetts General Hospital, Boston, Massachusetts, USA reported the results of IRONOUT HF during a late breaking session.  He reported that the primary endpoint, change in pkVO₂, did not differ between groups. Oral iron only modestly improved iron measures (i.e. Tsat increased from 19 to 22% p=0.003). Baseline Tsat was related to pkVO₂ and KCCQ and changes in Tsat correlated with changes in pVO2 over the course of the trial. Further analyses of biomarker samples are underway to understand the primary results (i.e. hepcidin levels in relation to responsiveness to oral iron).

High-dose oral iron minimally repleted iron stores and did not improve exercise capacity in HFrEF raising questions about the ability of oral iron therapies to be sufficient in heart failure patients.

In EFFECT-HF, researchers evaluated the efficacy of intravenous ferric carboxymaltose compared to usual care on exercise capacity in a prospective, randomized controlled, open-label, assessor-blinded, multicenter, two-arm, 24-week study in stable heart failure patients. Overall, 174 subjects were randomized in 9 countries.

Dirk J. Van Veldhuisen, University Medical Center Groningen, Groningen, Netherlands reported that the study met its primary endpoint, finding a significant difference of change in peak oxygen consumption from baseline to week 24 for those in the treatment group. Researchers said that patientss with chronic heart failure and iron deficiency treated with FCM can stabilize exercise capacity compared to those with standard of care whose exercise capacity worsened.

EFFECT-HF was sponsored by Vifor Pharma.

The authors of IRONOUT HF report support from Abbott Vascular, Novartis, Stealth, Shape Systems, Amgen, AstraZeneca, Merck and Novartis.