The FAIR-HF (Ferinject Assessment in Patients with Iron Deficiency and Chronic Heart Failure) trial, reported on by Anker and colleagues in this issue of the Journal,9 is a multicenter trial that evaluated the efficacy of intravenous-iron infusion on symptoms and submaximal exercise capacity in a cohort of patients with mild or moderate heart failure due to left ventricular systolic dysfunction (NCT00520780). The trial enrolled 459 patients with NYHA functional class II or III symptoms, a depressed left ventricular ejection fraction, and documented iron deficiency. According to a randomized, placebo-controlled design, patients were assigned to receive 200 mg of intravenous iron or infused saline weekly until their iron stores were replete. Then, intravenous iron or placebo infusions were continued every 4 weeks up to week 24. The primary end points were the self-reported Patient Global Assessment and the NYHA functional class at week 24. Secondary end points included the distance on the 6-minute walk test and health-related quality-of-life validated surveys at weeks 4, 12, and 24.
The two groups of patients were well matched regarding the baseline characteristics: overall, 82% had NYHA class III symptoms; the mean left ventricular ejection fraction was 32%; the mean serum ferritin level was 52 µg per liter in the ferric carboxymaltose group and 60 µg per liter in the placebo group; and 50% of patients had anemia. Ferric carboxymaltose therapy rapidly increased ferritin levels to be within the normal range; a modest increase in the serum hemoglobin level was seen in patients who had anemia (mean [±SE] increase, 9.1±2.2 g per liter; P<0.001) but not in patients who did not have anemia. The administration of intravenous iron, as compared with placebo, convincingly improved the self-reported Patient Global Assessment (odds ratio, 2.5) and the NYHA functional class (odds ratio, 2.4). For the self-reported Patient Global Assessment, 50% of the treated patients reported that they were much or moderately improved, as compared with only 28% of the control patients. The degree of improvement in both end points was similar in patients with anemia and those without anemia. Furthermore, significant improvement in the secondary end points, including an increase of more than 30 m in the 6-minute walk distance, was also observed. There was also a nonsignificant trend toward fewer hospitalizations for cardiovascular reasons (hazard ratio, 0.53; 95% confidence interval, 0.25 to 1.09; P=0.08).
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Anemia and Iron Deficiency — New Therapeutic Targets in Heart Failure?
G. William Dec, M.D., New England Journal of Medicine
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N Engl J Med. 2009 Nov 17.
Ferric Carboxymaltose in Patients with Heart Failure and Iron Deficiency.
Anker SD, et.al.
BACKGROUND: Iron deficiency may impair aerobic performance. This study aimed to determine whether treatment with intravenous iron (ferric carboxymaltose) would improve symptoms in patients who had heart failure, reduced left ventricular ejection fraction, and iron deficiency, either with or without anemia. METHODS: We enrolled 459 patients with chronic heart failure of New York Heart Association (NYHA) functional class II or III, a left ventricular ejection fraction of 40% or less (for patients with NYHA class II) or 45% or less (for NYHA class III), iron deficiency (ferritin level <100 mug per liter or between 100 and 299 mug per liter, if the transferrin saturation was <20%), and a hemoglobin level of 95 to 135 g per liter. Patients were randomly assigned, in a 2:1 ratio, to receive 200 mg of intravenous iron (ferric carboxymaltose) or saline (placebo). The primary end points were the self-reported Patient Global Assessment and NYHA functional class, both at week 24. Secondary end points included the distance walked in 6 minutes and the health-related quality of life. RESULTS: Among the patients receiving ferric carboxymaltose, 50% reported being much or moderately improved, as compared with 28% of patients receiving placebo, according to the Patient Global Assessment (odds ratio for improvement, 2.51; 95% confidence interval [CI], 1.75 to 3.61). Among the patients assigned to ferric carboxymaltose, 47% had an NYHA functional class I or II at week 24, as compared with 30% of patients assigned to placebo (odds ratio for improvement by one class, 2.40; 95% CI, 1.55 to 3.71). Results were similar in patients with anemia and those without anemia. Significant improvements were seen with ferric carboxymaltose in the distance on the 6-minute walk test and quality-of-life assessments. The rates of death, adverse events, and serious adverse events were similar in the two study groups. CONCLUSIONS: Treatment with intravenous ferric carboxymaltose in patients with chronic heart failure and iron deficiency, with or without anemia, improves symptoms, functional capacity, and quality of life; the side-effect profile is acceptable.