SA JOURNAL OF DIABETES & VASCULAR DISEASE
DRUG TRENDS
VOLUME 10 NUMBER 3 • SEPTEMBER 2013
115
accelerated atherosclerosis, increased rates
of stenosis/re-occlusion and exaggerated
inflammation.’
The only real difference between
STEMI and non-STEMI ACS is that in the
former, the thrombus occludes the vessel
completely. This means that with STEMI
every second counts, whereas one can wait
before treating non-STEMI. ‘Symptoms of
STEMI are unreliable in those with diabetes,
and they may not present with classic chest
pain’, said Dr Khan.
‘When performing primary percutaneous
intervention (PCI), one should not use bare-
metal stents in diabetic patients, but rather
second-generation drug-eluting stents.
However, the “limos” drugs do not work as
well in diabetics as in non-diabetics, failing
to inhibit smooth muscle proliferation, so
paclitaxel is a better option.’ With regard to
adjunctive antiplatelet therapy, prasugrel is
more effective than clopidogrel in diabetics.
Many low- and middle-income countries
have a shortage of PCI facilities and
interventional cardiologists, which makes
addressing ACS in these environments
challenging, given that it requires prompt
action. ‘If PCI is not an option, fibrinolysis
is an alternative strategy. Further to this, the
patient can be transferred to a PCI-capable
facility for angiography and possible PCI if it
is still appropriate.’
People living with diabetes are considered
at high risk for non-STEMI and may be
asymptomatic. ‘Thirty per cent of patients are
hyporesponders to clopidogrel and in future,
ticagrelor – which will be launched next year
– will be a better option. As with diabetic
therapies, antiplatelet and antithrombotic
regimens are complex.’ People living with
diabetes are also more likely to have adverse
left ventricular remodelling, and this needs
to be borne in mind.
Hyperglycaemia during ACS is a powerful
predictor of in-hospital survival, and compli-
cations and so-called ‘stress hyperglycaemia’
is common in both diabetics and non-dia-
betics. Blood glucose control is therefore
imperative, but the challenge is to achieve
this without inducing hypoglycaemia, which
has its own cardiovascular risks in respect of
being arrhythmogenic and a precipitator of
ischaemia. Symptom status is not a reliable
predictor of ischaemia and provocative test-
ing is required to assess the total ischaemic
burden, which in turn predicts prognosis.
Summing up, Dr Khan observed that
all STEMI patients should be taken to the
catheterisation laboratory and that an early
invasive strategy is also associated with better
survival in non-STEMI. PCI with a drug-eluting
stent should be followed by dual antiplatelet
therapy for one year, and coronary artery
bypass grafting should be undertaken when
there is multivessel disease.
‘In developing countries, the progression
of insulin resistance to diabetes parallels that
of endothelial dysfunction to atherosclerosis.
Primary prevention, in the form of early
aggressive diabetes therapy, is therefore
important.’
Tailoring antidiabetes treatment in
the era of CVD risk management
Dr Rajendran Moodley, specialist physician
in private practice, Umhlanga
Diabetes management needs to move
beyond glucose control to embrace multiple
risk-factor intervention. ‘We need a broader
understanding of diabetes to achieve
integrated control of the condition. The
traditional glucocentric approach is no
longer appropriate,’ said Dr Moodley.
He too underscored the importance of
early intensive therapy, pointing out that
the apparently confounding results of the
ACCORD trial, in which it was shown to be
harmful, should not be overestimated. ‘The
patients in that study were predominantly
older individuals with a history of CVD
events and multiple risk factors. They were
therefore not representative of all diabetics.
Individualise the control and ensure
treatment that is aggressive but tailored
to each specific patient. When choosing
therapy, consider the mechanism of action,
the patient’s cardiovascular profile and any
pleiotropic effects the agent(s) may have.’
Paradigms will shift with newer
agents, and the incretins show promising
cardiovascular benefits, although some of
these have yet to be translated into clinical
practice. ‘There is evidence that the GLP-1
receptor agonists may have beneficial
effects on the myocardium and endothelial
function and, in high-risk patients, improve
left ventricular function. To improve control,
therapy must be intensive, integrated and
individualised,’ he concluded.
New antidiabetic drugs and safety:
an introduction to the LEADER
TM
trial
Dr Adri Kok, specialist physician in private
practice, Alberton
Diabetes drugs need to be safe and help
prevent CVD. The LEADER
TM
trial, currently
under way, is a five-year CVD outcomes
study evaluating the GLP-1 receptor agonist,
liraglutide. It is currently at the three-and-a-
half-year mark.
The trial population comprises people
living with diabetes over the age of 50 years
with a history of CVD events that puts them
at high risk. ‘So far we’re seeing effective
HbA
1c
control along with significant weight
reduction and an absence of hypoglycaemic
episodes. So there is safety, but not
necessarily fewer events. It will be interesting
to see what comes out.’
GLP-1: glucose lowering and beyond
Prof Jeffrey Wing, chief physician and
professor of Medicine, Charlotte Maxeke
Johannesburg Hospital
Prof Wing underscored the importance
of addressing overweight and obesity
in diabetes management. ‘Weight is a
composite target and the relationship
between body mass index (BMI) and
diabetes risk is well established. Weight is
also linked to other CVD risk factors and
co-morbidities, as well as being associated
with increased mortality rates.’
Routine lifestyle intervention has shown
little benefit in the medium to long term
in respect of cardiovascular outcomes.
‘The genetic component of obesity is
underestimated. The impact of genes is also
underplayed in type 2 diabetes itself, where
they have an important role.’
Bariatric surgery in the form of the Roux-
en-Y gastric bypass has shown remarkably
successful outcomes, with durable weight
reduction aswell asmetabolic, cardiovascular
and diabetes mortality benefits. ‘The risk of
developing diabetes in obese, non-diabetic
individuals was reduced, and blood pressure,
lipid levels and general cardiovascular
risk scores all improved. There’s no doubt
that surgery works and even though it’s
an expensive procedure initially, it’s been
shown to be cost effective in the long term.
So should it be universally available?’
Current guidelines, however, recommend
surgery only in specific patients after failed
medical treatment. Yet bariatric surgery
reduces appetite, increases satiety and
GLP-1 levels. The question then is, ‘Can this
be achieved without surgery?’
Yes, injectable GLP-1 analogues can
mimic what bariatric surgery can achieve.
Current evidence suggests that they bring
about weight reduction that is durable
and sustained. They provide a composite
