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CARDIOVASCULAR JOURNAL OF AFRICA • Volume 28, No 5, September/October 2017
334
AFRICA
parental iron showed clear short- to medium-term benefits,
leading to improved symptoms and quality-of-life measures and
less hospitalisation.
32,33,50-53
In the FAIR-HF study, patients were
randomised to parental iron or placebo and 50 versus 28%, and
47 versus 30% reported improved quality of life and New York
Heart Association (NYHA) class, respectively.
32
Similarly in the
FERRIC-HF study, 35 patients with congestive heart failure were
put on 16 weeks of intravenous iron or no treatment in a 2:1 ratio.
50
The NYHA functional class improved in eight patients (44%) in
the iron group versus no patients in the control group (
p
= 0.03).
In all these trials, parental iron was used as a supplement,
added to standard therapy on optimal pharmacological
treatment, which included a diuretic, a beta-blocker and/or an
angiotensin converting enzyme (ACE) inhibitor or angiotensin
receptor blocker (ARB) as determined by the investigator (unless
contra-indicated or not tolerated). Data on the efficacy of
parental iron remain undisclosed in SSA.
Dosage for parental iron therapy in HF
Table 5 provides the dosage for various types of parental iron
used in clinical trials, nine of which used parental ferric sucrose
(FSC),
24,52,54,56,57,61-63
two used parental ferric carboxymaltose
(FCM),
32,33
one study used both ferrics,
60
one used ferric
gluconate,
53
and one iron dextran.
55
In most of the studies,
the 200-mg weekly dose for parental FSC was applied in the
correction phase, with a maintenance period in some studies.
However, for parental FCM, it was given either as a total loading
dose to correction or a 200-mg weekly dose. There is therefore
a need to have a standardised dose for both parental FSC and
FCM, and to determine whether the same doses apply in SSA.
Treatment targets of parental iron therapy in HF
The target treatment levels are variable, ranging from
replenishment through maintenance to a predetermined period
of study or haemoglobin level. From the clinical perspective,
this needs to be carefully determined from additional studies,
for guideline implementation. The levels of haemoglobin for
initiation and cessation should also be properly studied, as
well as the period of maintenance or monitoring for those who
receive iron replenishment.
Long-term effects after parental iron therapy in HF
During treatment, intravenous iron seems to be relatively safe
with only a few side effects or adverse events, which can usually
be tolerated by the patients.
33,44
However, data are limited on the
long-term effects after this therapy is ended, such as undesirable
complications (iron overload or myocardial changes) several
years after therapy. It is also not known how long the replenished
iron store and improved clinical symptoms of HF are sustained
following parental iron therapy. A close follow up of patients
who received iron therapy, several months or years after therapy
may shed some light on the matter.
Excluded populations in parental iron therapy trials
Despite the significant progress made in the use of parental iron
in patients with HF and ID, most of the trials included patients
with heart failure with reduced ejection fraction (HFrEF) (EF
<
40 or 45%) and no data are available for patients with heart
failure with preserved ejection fraction (HFpEF). It is also
unclear whether this therapy could benefit patients with HF due
to valvular heart disease, obstructive cardiomyopathy, those with
Hb levels
<
9.5g/dl or > 13.5g/dl and iron deficiency. The findings
from these trials therefore cannot be generalised and must be
applied with caution in SSA populations.
Possible limitation of parental iron therapy in SSA
The high level of iron deficiency in a setting where infections,
haemoglobinopathies and malnutrition are common requires
special attention.
2
The role of parental iron therapy (and other
potential options) in SSA requires further justification before
implementation measures are considered. The TaHeF study,
along with a few other reports from SSA, have locally quantified
the magnitude of anaemia, as shown in Table 2.
2
TaHeF was the only study that characterised ID, which
resulted in a poor prognosis in HF patients. With this limited
regional data, further studies are needed to identify the
peculiarities of ID and other types of anaemia or nutritional
deficiencies (folate, vitamin B
12
) in HF in SSA and determine
whether the consequences are the same as in high-income
countries before any interventions (whether parental or oral) are
conducted or adopted.
Apart from epidemiological challenges, as explained above,
the other important limitation may be related to acceptance
of and adherence to parental iron. Across all studies done in
high-income countries, none looked at the level of adherence.
Even with oral therapy and other HF medication, the problem
of compliance in SSA is high and is mainly related to financial
constraints, limited access to health facilities, as well as limited
health education/awareness. Proper measures should therefore be
put in place to address this.
This approach also imposes a burden on the patient, with
increased clinic appointments and transportation costs, and
absence from work of people with already reduced mobility
and functional capacity. This may complicate the already
compromised health system with overloading of clinics and
administrative logistics. There is possibly a need to have an
accelerated iron-supplementation regimen, which would
shorten the duration, or look into the possibility of providing
parental iron for replenishment in the hospital ward, while
maintenance with oral iron is taken at home, with more widely
scheduled appointments.
53
Finally, parental iron is expensive
and administration to large populations of HF patients may
not be feasible, particularly in countries with limited healthcare
resources.
Possible role of oral iron therapy in SSA
Oral iron supplementation is an established therapy for treating
iron deficiency in a range of medical conditions but it has not
been widely tested in HF patients. It remains promising in
resource-limited settings because (1) newer ferrous sulphate
preparations may be better absorbed than the older ferrous
sucrose; (2) the pathophysiology or iron deficiency may differ
geographically; and (3) oral iron supplementation is inexpensive.
Preliminary studies (Table 6) on randomised clinical trials