FERRIC CARBOXYMALTOSE IN PATIENTS WITH HEART FAILURE AND IRON DEFICIENCY(FAIR-HF)Anker SD, Colet JC, Filippatos G, Willenheimer R, Dickstein K, Drexler H et allJournal reading, 26 January 2010Ronald David Martua NababanN Engl J Med 2009;361:2436-48

iron deficiency with or without anaemia, may be associated with reduced functional capacity

BackgroundPatients with heart failure may be prone to the development of iron deficiency

Patients who had heart failure, reduced LVEF, and iron deficiencyWith anemia Without anemia.FAIR - HF

Inclusion

Chronic heart failure of NYHA class II or III, NYHA class II LVEF < 40% NYHA class III LVEF < 45% Hb 95 - 135 g per liter, Iron deficiency Ferritin level

Procedures

Ferritin level exceeded 800 g per liter or500 and 800 g per liter with a transferrin saturation of more than 50%Hb level was higher than 160 g per literRestartedferritin level < 400 g per liter, the transferrin saturation < 45%, Hb < 160 g per literSevere anemia (Hb 90 g/lt) study discontinued.

Primary End Point :The self-reported Patient Global Assessment & NYHA functional class at week 24Secondary end Point :The self-reported Patient Global Assessment and NYHA at week 4 & 12Distance on the 6-minute walk test The overall score on the Kansas City Cardiomyopathy questionnaireThe European Quality of Life5 Dimensions (EQ-5D) Visual Analog ScaleStudy End PointSafety end pointsSerious and Nonserious adverse events, Hospitalization, and Death, as assessed up to week 26

DiscussionTreatment with ferric carboxymaltose for 24 weeks in patients who had chronic heart failure and iron deficiency with or without anemia improved symptoms, functional capacity, and the quality of life. Treatment with ferric carboxymaltose was not associated with an unacceptable side-effect or adverse-event profile. These results were consistent across all prespecified subgroups and were confirmed by the observed improvements in distance on the 6-minute walk test distance and in scores on the health-related quality-of-life questionnaires.

The treatment with ferric carboxymaltose was beneficial to both patients with anemia and those without anemia. This suggests that iron deficiency is a valid independent therapeutic target. Iron metabolism in patients with chronic illness merits a more detailed investigation to unravel the reasons why the correction of iron deficiency can result in symptomatic improvements even in the absence of a change in hemoglobin. Discussion

Conclusion In stable, symptomatic, ambulatory patients with chronic heart failure, an impaired left ventricular ejection fraction, and iron deficiency, treatment with ferric carboxymaltose over a 24-week period improves symptoms, physical performance, and the quality of life and has acceptable side-effect and adverse-event profiles.

The benefit was seen in patients with anemia and in those without anemia.

Critical appraisal1. Are the result of this individual study valid? YesWas the assignment of patient to treatment randomized? YesWas the randomized concealed ? YesWere the group similar at the strat of the trial? YesWas the follow up of patient sufficiently long and complete ? YesWere all patient analyzed in the group to which they were randomized ? YesWere patient, clinicians and study personel kept blind to treatment? YesWere group treated equally, apart from the experimental therapy? Yes

Are the valid results of this individual study important?We would need to treat 4 patients like those on the trial with ferric carboxymaltose to have improvement according to the Patient Global Assessment, and need to treat 5 patients like those on the trial with ferric carboxymaltose to have improvement NYHA functional class

This study is important

End pointCEREERRelative risk reduction(CER-EER) / CERAbsolute risk reduction(CER-EER)Number need to treat (NNT)(1/ARR)Self-reported Patient Global Assessment 50280.44220.04 = 4%Improvement NYHA functional class47300.36170.05 = 5%

Are the valid important results of this individual study applicable to our patient?

Is our patient so different from those in the study that its results cannot apply? No. The baseline characteristicc are similar.Is the treatment feasible in our setting? Yes.What our patients potential benefits and harms from the therapy? The potential benefits and harms will similiar as this study groupWhat are our patients values and expectations of both the outcome we are trying to prevent and the treatment we are offering? The treatment with ferric carboxymaltose will help our patients and the adverse events not different.

Thank you

Total iron deficit (TID) can be calculated using the Ganzonis formula

Ganzonis formula: TID (mg) = Weight (kg) (Ideal Hb - Actual Hb) (g/dL) 0.24 + depot iron (500 mg).

Intravenous iron in inflammatory bowel disease , World journal of gastroenterology 2008

The Kansas City Cardiomyopathy Questionnaire is a 23-item, self-administered instrument that quantifies physical function, symptoms (frequency, severity and recent change), social function, self-efficacy and knowledge, and quality of life.

Absorbed IronExcretionStorage iron (Liver,Spleen,Bone marrow) 20-30%Transport iron(Plasma) 0.05 - 0.18mg%Functional Tissue iron (Parenchymal iron) (Cellular Oxidation) 5%Myoglobin3-15 %Hematopoietic organsBlood Hb70%

Iron Deficiency AnaemiaOverview of Iron HomeostasisWith permission from Andrews NC. Blood. 2008;112:219-230.