DRUG TRENDS
SA JOURNAL OF DIABETES & VASCULAR DISEASE
40
VOLUME 7 NUMBER 1 • MARCH 2010
she said.
The current target is a blood pressure
below 140/90 mmHg in healthy individu-
als and below 130/80 mmHg in diabetics
and those with chronic kidney disease.
‘However, there is increasing evidence that
high-normal blood pressure is associated
with increased cardiovascular risk, and we
are currently considering a blood pressure
higher than 135/85 mmHg on repeated
testing as diagnostic of hypertension.’
Masked hypertension, which Prof Touyz
described as reverse white-coat hyperten-
sion, is an additional challenge. ‘Its prog-
nosis in respect of cardiovascular event risk
is as high as that with uncontrolled essen-
tial hypertension’, she said.
Because hypertension affects many sys-
tems and is associated with a variety of
diseases, it has an immense impact on a soci-
ety’s disease burden. ‘The benefits of treat-
ment have been proven and the younger
you treat patients, the better the outcome.
The ultimate goal is to optimally reduce
cardiovascular risk by treating to target.’
Lifestyle modification remains the cor-
nerstone of treatment. The 2009 guide-
lines recommend: restricting salt intake to
<
2 300 mg/day; weight loss to achieve a
BMI < 25 kg/m
2
; alcohol restriction (
≤
two
drinks/day); smoking cessation; 20 minutes
of exercise four times a week; and a waist
circumference
<
102 cm in men and
<
88
cm in women. The so-called DASH diet
(Dietary Approach to Stop Hypertension)
emphasises fresh fruit and vegetables, fish
and low-fat dairy products.
Is there evidence that these measures
have an impact? ‘Yes!’ said Prof Touyz.
‘Lifestyle modification, especially the com-
bination of the DASH diet and sodium
restriction, has a significant impact on
blood pressure, independent of drug ther-
apy. The various lifestyle measures have
also been shown to have an additive effect.’
Early use of more than one first-
time drug
Even a modest decrease of 2 mmHg is
beneficial. However, drug treatment may
be necessary – and if lifestyle measures are
not enough, two first-line drugs should be
chosen as initial therapy. ‘There are many to
choose from, and patients generally need
two or more to obtain good blood pres-
sure control. The choice of drugs should be
guided by a patient’s other diseases, risk
factors and whether or not there is target-
organ damage’, said Prof Touyz.
The current CHEP guideline update was
guided by the findings of three recent large
clinical trials, namely, ONTARGET, HYVET
and ADVANCE. Based on the findings of
ONTARGET, the guideline discourages the
use of a combination of ACE inhibitors and
angiotensin receptor blockers (ARB). The
combination should only be considered in
closely monitored patients with advanced
heart failure or proteinuric nephropathy
under specialist care.
The findings of HYVET have led to the
recommendation that treatment of patients
over 80 years old with indapamide, with or
without perindopril, is beneficial and that
the therapeutic needs of elderly patients
should be assessed according to the same
criteria as those of younger patients.
ADVANCE found that blood pressure
lowering with perindopril/indapamide in
type 2 diabetics had a significant reno-
protective effect, independent of blood
pressure levels. As a result, the updated
guideline now recommends more intensive
blood pressure reduction in type 2 diabetics.
In summary, Prof Touyz underscored
that hypertension is a critical cardiovascu-
lar risk factor and often poorly controlled.
‘Even small decreases in blood pressure
can have large benefits. We need to get
patients to target using a combination of
education, lifestyle modification and indi-
vidualised pharmacotherapy. And while
we’re doing this we need to have patience
with our patients’, she concluded.
Fixed-drug combination in the
treatment of hypertension and
hyperlipidaemia in the developing
world
Prof YK Seedat, Emmeritus Professor, Uni-
versity of KwaZulu-Natal, Durban
The primary problem when it comes to
hypertension and hyperlipidaemia is not
incomplete treatment, but rather, no treat-
ment at all of those patients unknown to
the healthcare system. It’s obvious that it
would be highly beneficial if these patients
could be identified and provided with treat-
ment, possibly in the form of a fixed-drug
combination (FDC).
Prof Seedat defined an FDC as two or
more drugs in a single formulation, with
independent modes of action and syner-
gistic, additive and complementary effects.
‘Many consider FDCs essential to the treat-
ment of hypertension and yet there is lim-
ited empirical evidence to suggest that
they increase patient compliance and thus
outcomes, which is one of their presumed
advantages.’
Other advantages include increased
efficacy consequent on the complemen-
tary mechanisms, reduction of inadvertent
medication errors, fewer adverse events, a
single expiry date, lower production and
packing costs, and a broader spectrum
of response. Also, an FDC is often less
expensive than its components would be if
bought separately.
FDCs are not without potential disad-
vantages, however. Prof Seedat pointed
out that patients might be allergic to one
of the components (in which case the
combination should be discontinued and
replaced with single agents), dosing is
inflexible, and incompatible pharmacoki-
netics may result from differences in the
components’ elimination half-lives.
Allowing for these cautionary aspects,
Prof Seedat feels that FDCs carry a high
chance of benefit and a low chance of
causing harm. An FDC can combine medi-
cines that have antihypertensive, antiplate-
let and lipid-lowering effects, with the
potential for a marked improvement in
overall cardiovascular risk.
Citing the landmark 2003 ‘Polypill’
study published in the British Medical Jour-
nal, he noted its conclusion that a pill com-
bining a thiazide diuretic, beta-blocker and
ACE inhibitor (all at half the standard dose)
with aspirin and folic acid could poten-
tially reduce cardiovascular disease by over
80%. ‘It could therefore have enormous
potential in developing countries, which
is where 80% of chronic disease deaths
occur’, he said.
‘The WHO Bulletin in 2005 endorsed
the view that a polypill could be of ben-
efit to those with chronic disease, and in
2007 the India Polypill study supported the
British Medical Journal’s study findings in a
developing-world setting’, he concluded.
Fasting plasma arginine
concentrations and ambulatory
blood pressure
Dr Geoff Candy, University of the Witwa-
tersrand, Johannesburg
Hypertension affects six million South
Africans and costs the healthcare system
R200 million per annum. Dr Geoff Candy
