CARDIOVASCULAR JOURNAL OF AFRICA • Vol 22, No 4, July/August 2011
224
AFRICA
ARBs for cardiovascular and renal protection in high-risk patients
The contribution of recent trials such
as the extensive ONTARGET (ONgoing
Telmisartan Alone and in combination
with Ramipril Global Endpoint Trial)
‘a thorough, double-blind, prospec-
tive, randomised trial, which documents
the equal-outcome efficacy of an ARB
(telmisartan) and an ACE inhibitor in a
high-risk population’ is noted in a recent
meta-analysis of ARBs.
1
Among ARBs, telmisartan is further
differentiated by both its pharmacokinetic
and pharmacodynamic properties.
2
It has
a longer half-life and higher lipophilicity
than other agents in the class.
Focus on ONTARGET: cardio-
vascular protection in high-risk
patients without heart failure
The findings from the ONTARGET study
showed that telmisartan 80 mg per day
was as efficacious as the proven dosage
of ramipril (10 mg/day) in reducing the
risk of cardiovascular death, myocardial
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.
3
The ONTARGET study was designed
to measure the effects of ramipril,
telmisartan or a combination of the two
drugs in patients over the age of 55
years. It recruited and randomised 25 620
patients over 18 months at 733 centres
in 40 countries, including South Africa.
These patients all had coronary, periph-
eral or cerebrovascular disease or diabetes
with end-organ damage.
Characteristics of the patients were
similar in the three groups, which includ-
ed 27% women, 75% of patients had
coronary artery disease, 69% had hyper-
tension, 38% had diabetes and 21% had
stroke or transient ischaemic attack. The
mean age was 66.4 years. Interestingly,
while the majority of patients (70%) were
Caucasian/European, there was a good
representation of patients of Asian (15%),
Latin (9%) and blackAfrican (2%) origins.
Prof Yusuf, professor of Medicine and
director of the Population Health Research
Institute at McMaster University,
Ontario, Canada, pointed out when the
ONTARGET results were announced,
that this comparative head-to-head trial
of telmisartan 80 mg and ramipril 10 mg
was designed to establish equivalence
firstly (in statistical terms referred to as
non-inferiority), and to provide clinically
relevant data by choosing the usual dose
of telmisartan and the proven dose of
ramipril, based on the HOPE study. In
addition, ONTARGET sought to answer
the provocative question of whether the
combination of an ACE inhibitor and an
angiotensin receptor blocker would work
for these high-risk patients and provide
further benefit, as it does for patients with
heart failure.
Comparison of telmisartan and
ramipril
The ONTARGET results showed that
telmisartan (Micardis) therapy was as
effective as ramipril in each component of
the composite outcome, which included
death from cardiovascular causes, myocar-
dial infarction, stroke or hospitalisation
for heart failure. The composite outcome
occurred in 1 412 (16.5%) patients in the
ramipril-alone treated group compared to
1 423 (16.7%) patients in the telmisartan-
alone treated group.
There was no significant difference in
the total number of deaths between the
ramipril and telmisartan groups; 1 014
and 989 deaths, respectively. ‘Telmisartan
was clearly non-inferior, as the confi-
dence interval for the relative risk of the
primary outcome was well below the prior
established upper boundary of equiva-
lence’, Prof Yusuf stressed. With regard to
secondary outcomes, there were also no
significant differences in the telmisartan-
alone compared to the ramipril group.
Telmisartan therapy did, however,
result in slightly improved blood pressure
control, with somewhat lower blood pres-
sure levels than those achieved in the rami-
pril-alone group. Before the run-in period,
the mean blood pressure was 141.8/82.1
mmHg. At six weeks, the mean blood
pressure was reduced by 6.4/4.3 mmHg
in the ramipril-alone group, compared to
6.9/5.2 mmHg in the telmisartan-alone
group. Although the blood pressures in
the telmisartan group remained slightly
lower throughout the study, the differ-
ence was not significant, and adjust-
ment for this did not affect outcomes.
‘This study is of significant clini-
cal importance because it demonstrates
that telmisartan is an effective and safe
alternative to ramipril. This means both
patients and physicians have choices and
can use telmisartan where appropriate
with a high degree of confidence. While
we cannot be sure what we will see with
other ARBs, with telmisartan, clinicians
now know its efficacy and its tolerability’,
Prof Yusuf concluded.
Renal protection
The evidence supporting RAS blockade,
and especially the use of ARBs in patients
with type 2 diabetes and incipient and
overt nephropathy continues to grow.
The IncipieNT to Overt Angiotensin
II receptor blocker, Telmisartan, Investi-
gation On type 2 diabetic Nephropathy
(INNOVATION)
4
study has shown that
telmisartan delayed the transition from
incipient to overt nephropathy in Japanese
type 2 diabetes subjects, an effect that
was only partly related to blood pressure
control.
A clinical study conducted in patients
with type 2 diabetes and overt protein-
uria compared the renoprotective effect
of telmisartan with that of losartan on
a background of antihypertensive inter-
vention as required to ensure similar
blood pressure control [A trial to compare
telmisartan 40 mg titrated to 80 mg versus
losartan 100 mg in hypertensive type 2
DiabEtic patients with Overt nephropathy
(AMADEO)].
5
In this one-year, prospec-
tive, double-blind study, telmisartan
provided greater reduction in proteinuria
compared with losartan.
Prof George Bakris of the Department
of Medicine, Rush University Centre,
Illinois, USA, pointed out that the ulti-
mate test of the benefit of an antihyper-
tensive agent is its ability to reduce renal
and cardiovascular endpoints.
6
J Aalbers, Specialist Assignments Editor
1.
Bangalore S, Kumar S, Wetterslev J,
Messerli FH.
Br Med J
2011;
342
: d2234.
DOI: 10.1136/bmj.d2234.
2.
Munger MA.
Pharmacy Therapeut
2011;
36
(1): 22–40.
3.
ONTARGET proves telmisartan efficacy
compared to ramipril in cardiovascular
protection of patients at high risk and with-
out heart failure.
Cardiovasc J Afr
2008;
19
(2): 108–109.
4.
The Innovation Study Group.
Diabetes Care
2007;
30
(60): 1–2.
5.
Bakris G,
et al
.
Kidney Internal
May 2008.
DOI: 10.1038//ki.2008.204.
6.
Cardiovasc J Afr
2007;
18
: 337–340.
