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 all
N Engl J Med 2009;361:2436-48

Journal reading, 26 January 2010

Ronald David Martua Nababan

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

Background

Patients with heart failure may be prone

to the development of iron deficiency

Four small studies correction of iron

deficiency with the use of intravenous
iron in patients with chronic heart failure
may result in clinical benefits.

FAIR - HF
Patients
Patients who
who had
had heart
heart failure,
failure, reduced
reduced LVEF,
LVEF, and
and iron
iron deficiency
deficiency

With anemia
Without anemia.

Patients

Inclusion
heart failure of
NYHA class II or III,

Exclusion

Chronic

NYHA class II LVEF < 40%

NYHA class III LVEF < 45%

Hb

95 - 135 g per liter,

Iron deficiency
Ferritin level <100 g/lt
100 - 299 g/liter, if the
transferrin saturation <20%)

Uncontrolled hypertension,
other clinically significant
heart disease
inflammation
Impaired liver
Impaired renal function.

Procedures

Ferritin level exceeded 800 g per liter or

500 and 800 g per liter with a
transferrin saturation of more than 50%

Discontinued and
placebo
was given instead

Hb level was higher than 160 g per liter

Restarted
ferritin level < 400 g per liter,
the transferrin saturation < 45%,
Hb < 160 g per liter

Reassed

Severe anemia (Hb 90 g/lt) study discontinued.

Primary End Point :

The self-reported Patient Global Assessment
& NYHA functional class at week 24

Secondary end Point :

The self-reported Patient Global
Assessment and NYHA at week 4 & 12
Distance on the 6-minute walk test
The overall score on the Kansas City
Cardiomyopathy questionnaire
The European Quality of Life5 Dimensions
(EQ-5D) Visual Analog Scale

Safety end points

Serious and Nonserious adverse events,
Hospitalization, and Death,
as assessed up to week 26

Study End
Point

Discussion

Treatment 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-oflife questionnaires.

Discussion

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.

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 appraisal
1. Are the result of this individual study valid? Yes

Was the assignment of patient to treatment randomized?

Yes
Was the randomized concealed ? Yes
Were the group similar at the strat of the trial? Yes
Was the follow up of patient sufficiently long and complete
? Yes
Were all patient analyzed in the group to which they were
randomized ? Yes
Were patient, clinicians and study personel kept blind to
treatment? Yes
Were group treated equally, apart from the experimental
therapy? Yes

Are the valid results of this individual study

important?
End point

CER

EER

Relative risk
reduction
(CER-EER) /
CER

Absolute
Number need
risk
to treat (NNT)
reduction
(1/ARR)
(CER-EER)

Self-reported Patient
Global Assessment

50

28

0.44

22

0.04 = 4%

Improvement NYHA
functional class

47

30

0.36

17

0.05 = 5%

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

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?

Is the treatment feasible in our setting? Yes.

What our patients potential benefits and harms from the
therapy?

No. The baseline characteristicc are similar.

The potential benefits and harms will similiar as this study group

What 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, selfadministered instrument that quantifies
physical function, symptoms (frequency,
severity and recent change), social
function, self-efficacy and knowledge,
and quality of life.

Absorbed Iron

Excretion

Transport iron
(Plasma)
0.05 - 0.18mg%

Storage iron (Liver,Spleen,Bone

marrow) 20-30%

Myoglobin
3-15 %

Hematopoietic organs
Functional Tissue iron
(Parenchymal iron) (Cellular
Oxidation)
5%

Blood Hb
70%

Iron Deficiency Anaemia

Overview of Iron Homeostasis

With permission from Andrews NC. Blood. 2008;112:219-230.