CARDIOVASCULAR JOURNAL OF AFRICA • Vol 21, No 5, September/October 2010
AFRICA
291
Special Report
Reaching target LDL cholesterol has become more affordable with launch of ezetimibe/
simvastatin combination in South Africa
An affordable addition to the clinician’s
choice of LDL cholesterol-lowering agents
has become available in South Africa.
Ashley Pearce, CEO of Merck Sharpe &
Dohme, South Africa, and president of
the Pharmaceutical Industry Association
of South Africa (PIASA) emphasised the
need to increase accessibility to innovative
medicines for chronic diseases in South
Africa.
Speaking at the launch of INEGY,
Mr Pearce said, ‘After four to five years
of deliberations within MSD, a very
competitively priced combination tablet
of ezetimibe (10 mg) with simvastatin has
been launched in South Africa. We hope
that clinicians and funders will make use
of this opportunity to reduce cholesterol
levels to the internationally recommended
lower levels, particularly for high-risk
patients where LDL cholesterol levels
below 2.4 mmol/l are appropriate.’
Dr Dirk Blom, senior specialist at
the Groote Schuur Hospital Lipid Clinic
confirmed the value of this combina-
tion therapy in daily clinical practice at a
meeting of clinicians held in Cape Town
recently. Early clinical trials using statins
for both primary and secondary preven-
tion of coronary artery disease (CAD)
have shown that for every 1-mmol/l reduc-
tion in lipid levels, there is a correspond-
ing 21 to 24% reduction in coronary artery
disease and vascular events.
‘Initial trials lowered LDL cholester-
ol by approximately 30% but signifi-
cant residual risk remained. One of the
approaches to lowering residual risk has
been more aggressive LDL cholesterol
reduction. The recent JUPITER study
1
of rosuvastatin in primary prevention in
patients with an LDL cholesterol below 3.6
mmol/l and raised hs-CRP levels showed
that LDL cholesterol could be lowered
to mean levels of 1.42 mmol/l safely
and with benefit’, Dr Blom pointed out.
‘The combination of a statin and
ezetimibe in a single tablet potently reduc-
es LDL cholesterol via the dual mecha-
nisms of reduced cholesterol synthesis
and absorption. This combination can be
very useful for patients who tolerate stat-
ins poorly, with statin-related myalgia
being the commonest dose-limiting side
effect. Ezetimibe is also very useful if the
baseline LDL cholesterol is very high or
when a very low LDL cholesterol target
has been set.’
‘Doubling the statin dose only results
in a further 6% reduction in LDL choles-
terol levels, and reaching LDL cholesterol
targets often requires multiple doublings
which not all patients are able to toler-
ate. In this situation ezetimibe is a very
useful add-on medication to background
statin therapy, as adding ezetimibe further
lowers LDL cholesterol to approximately
the same degree as three doublings of the
statin dose, without significantly increas-
ing side effects’, he said.
‘The EASE study
2
where ezetimibe
was added to existing statin therapy
showed a further 20 to 25% reduction in
LDL cholesterol levels. The combination
of ezetimibe and the statin was well toler-
ated. Ezetimibe’s action is mainly on the
LDL cholesterol, although it does increase
HDL cholesterol marginally and lowers
triglycerides modestly.’
In addressing residual risk of patients
on statin therapy, Dr Blom indicated that
clinicians would need to be smarter at
addressing the different components of
the lipid profile, such as HDL cholesterol
levels and increased triglycerides. ‘With
other newer agents soon to come on the
market in SouthAfrica, clinicians will have
a wider compendium of agents to choose
from. While the evidence base for cardio-
vascular protection is strongest for statins,
the complementary evidence is substantial
for cardiovascular event reduction from
LDL cholesterol lowering, generally using
agents other than statins’, Dr Blom noted.
‘Despite the negative results of lipid
lowering with added ezetimibe on the
progression of aortic stenosis in the SEAS
study, and the better effect of niacin on
carotid intima–media thickness compared
to ezetimibe in the ARBITER-6 study’,
Dr Blom commented, ‘I feel confident to
use ezetimibe when additional lowering
of LDL cholesterol is required. However,
the outcome study of ezetimibe therapy
(IMPROVE-IT) is eagerly awaited. This
study will provide data on the safety and
efficacy of even lower LDL cholesterol
targets and will finally answer the question
whether lowering LDL cholesterol with
ezetimibe improves outcomes to the same
extent as seen with other LDL-lowering
therapies, especially statins.’
‘The recruiting of the 18 000 patients
needed for this study has recently been
completed and results should be available
in 2013, as the protocol requires a two-
year treatment period. The SEAS study
also reported higher cancer rates in the
ezetimibe arm, but analysis of much larger
datasets from ongoing trials indicated that
the findings in SEAS were likely due to
chance and not a true drug-induced effect.
This conclusion is supported by extensive
pre-clinical data in which no carcinogenic-
ity signal was observed.’
J Aalbers, Special Assignments Editor
1. Ridker PM, Danielson E, Fonseca FA, Genest
J, Goto AM Jr, Kastelen JJ, Koenig W,
et al
.
N Engl J Med
2008;
359
(21): 2195–2207.
E-pub Nov 9 2008.
2. Pearson TA, Denke MA, McBride PE,
et al
.
Mayo Clin Proc
2005;
80
(5): 587–595.
The ezetimibe/simvastatin combination has been
flat priced at the different simvastatin levels. The
combination is indicated as adjunctive therapy
to diet for the reduction of elevated total choles-
terol (total C), low-density lipoprotein cholesterol
(LDL-C), apolipoprotein B (Apo B), triglycerides
(TG) and non-high-density lipoprotein choles-
terol (non-HDL-C), and to moderately increase
high-density lipoprotein cholesterol (HDL-C)
in patients with primary heterozygous familial
and non-familial hypercholesterolaemia or mixed
hyperlipidaemia. It is also indicated for the reduc-
tion of elevated total C and LDL-C levels in
patients with homozygous familial hypercholes-
terolaemia (HoFH).
Dosage and directions for use
The patient should be placed on a standard choles-
terol-lowering diet before receiving the combi-
nation and should continue on this diet during
treatment. The dosage should be individualised
according to the baseline LDL-C level, the recom-
mended goal of therapy, and the patient’s response.
The tablet should be taken as a single daily dose in
the evening, with or without food.
The dosage range is 10/10 mg/day to 10/80
mg/day. The recommended usual starting dose
is 10/20 mg/day. Initiation of therapy with 10/10
mg/day may be considered for patients requiring
less aggressive LDL-C reductions. Patients who
require larger reductions in LDL-C (
>
55%) may
be started at 10/40 mg/day. After initiation or
titration of the combination, lipid levels may be
analysed after two weeks and dosage adjusted, if
needed.
For further information, contact MSD on
011 655-3143.
