VOLUME 8 NUMBER 1 • MARCH 2011
31
SA JOURNAL OF DIABETES & VASCULAR DISEASE
OPINIONS IN HYPERTENSION MANAGEMENT
Opinions in Hypertension Management
Improving hypertension control in patients with diabetes: the case for
telmisartan-based therapy
S
trategies to improve hypertension con-
trol are clearly warranted in light of the
frequently expressed view that only 50% of
treated hypertensive patients are able to meet
their target blood pressure levels.
While data from the USA has shown
improved control over recent years, a study in
2008 of South African general medical practice
(private sector) showed that 61% of patients
reached their target blood pressure levels. If
the even-stricter target blood pressure levels of
130/80 mmHg were applied to those patients
with diabetes who needed to reach and main-
tain these lower levels, only 40% of patients
were successfully treated.
1
In primary-care, public-sector facilities in
South Africa, special efforts to improve hyper-
tension management have shown that 68%
of patients treated for their hypertension can
achieve their targeted blood pressure levels.
2
Without these intensive programmes, how-
ever, hypertension control in the South African
public sector is likely to be much less effective
and lower than in the well-serviced private
sector.
Reducing the cardiovascular and renal con-
sequences of hypertension is dependent on
sustained, long-term blood pressure control,
implying that patient compliance is also a key
factor for success. The physician’s choice of
effective therapy will take this aspect fully into
account and he/she will adopt approaches that
will sustain patient compliance.
Modern therapeutic agents that block the
renin–angiotensin–aldosterone system (RAAS)
and protect target organs without causing
compliance-reducing symptoms should be
the first choice in at-risk diabetic patients with
hypertension.
Achieving sustained blood pressure
control
Once-a-day dosage
Patients typically prefer to take their medica-
tion in the morning as part of their everyday
routine. Compliance is improved by once-daily
medication and physicians are keen to ensure
that the prescribed antihypertensive medica-
tion meets the criteria of full 24-hour control
and provides cover for the early morning rise
in blood pressure. This rise in blood pressure
is due to both orthostatic changes and the cir-
cadian rhythm of the RAAS system. It is also
linked to an increased risk of cardiovascular
events during the early morning hours.
3
Accurate assessment of blood pressure
control is determined by self-measurement of
blood pressure or by automated ambulatory
24-hour measuring devices. The MICARDIS
Community Access Trial of Telmisartan in
the primary-care setting (MICCAT-2)
4
study
showed that telmisartan alone or in combina-
tion with HCTZ produced significant reduc-
tions in blood pressure, which extended into
both day and night time. Telmisartan reduced
systolic and diastolic blood pressure (SBP/DBP)
by 17.2/10.1 mmHg in the first four hours
post-awakening in patients whose early morn-
ing blood pressure rose more than 30 mmHg
prior to therapy.
ARB efficacy versus ACE inhibitors
ARBs are a good choice for hypertensive
patients with the metabolic syndrome (associ-
ated obesity) and there are compelling indica-
tions for their use in post-myocardial infarction,
left ventricular hypertrophy, chronic kidney dis-
ease, type 2 diabetes with microalbuminuria or
albuminuria, for ACE-intolerant patients and
for the secondary prevention of stroke.
5
The evidence for therapeutic equivalence
of telmisartan versus ACE inhibitors resides in
direct major comparison trials with ramipril and
perindopril. In the PRISMA-1 study (Prospec-
tive Randomised Investigation of the Safety
and efficacy of MICARDIS versus ramipril) also
conducted in South Africa, 1 613 hypertensive
patients were treated either with temisartan
40–80 mg or ramipril (uptitrated from 2.5–10
mg) in the morning, and resulting blood pres-
sure was evaluated using ambulatory blood
pressure monitoring.
Telmisartan provided more effective blood
pressure lowering in this study and was partic-
ularly more efficient in the last six hours of the
24-hour dosing interval. Similar results were
obtained by PRISM-2, which was conducted
in the USA and Canada. A pooled analysis of
both trials also showed a greater blood pres-
sure lowering with telmisartan (–14.1/–9.6 vs
–11.1/–7.2 mmHg).
6
In a double-blind study
of telmisartan 80 mg versus perindopril 4 mg,
similar results in blood pressure lowering were
obtained but telmisartan resulted in lower
diastolic blood pressures over the last eight
hours of therapy. Other studies versus lisinopril
produced similar results.
Telmisartan is the only ARB that has dem-
onstrated therapeutic equivalence to the ACE
inhibitor ramipril in hypertensive patients at
increased vascular risk. The patient popula-
tion in this study (ONTARGET) is of particular
interest as it is representative of the majority of
hypertensive patients seen in everyday clinical
practice.
The findings from this study showed that
telmisartan 80 mg per day was as efficacious
as the proven dosage of ramipril (10 mg/day)
in reducing risk of cardiovascular death, myo-
cardial infarction, stroke and hospitalisation for
heart failure in a broad cross section of high-
risk cardiovascular patients. It achieved these
results with far fewer side effects, resulting
in significantly fewer patients discontinuing
therapy.
Choosing telmisartan over other
ARBs: the evidence
Pharmacological evidence of telmisartan’s effi-
cacy in terms of blocking the angiotensin II
type 1 receptor is accumulating. A recent Japa-
nese study of constructed models of ARB mol-
ecules has found that the delta lock structure
of telmisartan offers a superior fit to the recep-
tor, compared to the other ARBs.
7
This fit may
explain the highest lipophilicity, the greatest
volume distribution and the strongest binding
affinity of telmisartan to the type 1 receptor
when compared to other ARBs. This receptor
affinity is likely to contribute to the clinical evi-
dence for telmisartan’s greater blood pressure
lowering compared to other ARBs, particularly
losartan and valsartan.
8-10
Choosing the combination of
telmisartan + HCTZ
Blood pressure control in some patients is
ineffective with just monotherapy, and com-
binations of antihypertensive agents offer an
opportunity to intensify treatment without
adding to the pill load.
In African patients where there may be evi-
dence of less involvement of the RAAS system,
the initial choice in the public sector is often
a diuretic. A recent study in KwaZulu-Natal
looked at prescribing habits in 54 public-sector
hospitals in this region and compared this to
supply data and to the SA Hypertension Guide-
lines.
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