CARDIOVASCULAR JOURNAL OF AFRICA • Vol 24, No 8, September 2013
340
AFRICA
Drug Trends in Cardiology
Novo Nordisk Incretin and Cardiovascular Summit, Durban, June 2013
Acute coronary syndrome in
diabetes: how do we improve
clinical outcomes?
Dr Sajidah Khan, principal specialist in
cardiology, Wentworth and Albert Luthuli
central hospitals, Durban
Acute coronary syndrome (ACS) in
diabetics is associated with higher
mortality rates, higher morbidity and more
co-morbid conditions. ‘Type 2 diabetes is
more than hyperglycaemia. The unified
pathophysiology of oxidative stress and
subclinical inflammation drives both
diabetes and cardiovascular disease (CVD),
and diabetics have accelerated rates of
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 rath-
er 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 coun-
tries have a shortage of PCI facilities and
interventional cardiologists, which makes
addressing ACS in these environments chal-
lenging, 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 power-
ful predictor of in-hospital survival, and
complications and so-called ‘stress hyper-
glycaemia’ is common in both diabetics
and non-diabetics. Blood glucose control is
therefore imperative, but the challenge is to
achieve this without inducing hypoglycae-
mia, 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 testing 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 multi-vessel
disease.
‘In developing countries, the progression
of insulin resistance to diabetes parallels
that of endothelial dysfunction to athero-
sclerosis. Primary prevention, in the form of
early, aggressive diabetes therapy is there-
fore important.’
Hypoglycaemia and cardiovas-
cular outcomes in diabetes
Prof Wolfgang Schmidt, chief of GI/
Hepatology and Diabetes Services and
director of the Department of Medicine,
St Josef-Hospital, Ruhr-University Medical
School, Bochum, Germany
Hypoglycaemia is an important confounder
in the management of diabetes, and glycae-
mic control is only part of the story. To
achieve an overall favourable outcome also
requires control of CVD risk factors and an
avoidance of weight gain and hypoglycae-
mic episodes.
Multiple studies have shown the benefits
of good early glycaemic control and its
association with a lower CHD event rate. Its
legacy effect confers significant benefit 10
to 15 years later. The challenge in achieving
this favourable scenario lies in attaining
glycaemic control, lowering lipid levels and
blood pressure and avoiding hypoglycaemia
while not doing harm.
Intensive intervention in diabetes and
better glycaemic control often come at the
price of increased weight gain and more
hypoglycaemic episodes, which is a bad
risk–benefit ratio. Certain patients are at
particular risk, including the elderly, those
with diabetes of longer duration and/or a
high baseline HbA
1c
level, and patients with
renal dysfunction or peripheral neuropathy.
Severe hypoglycaemic events are associ-
ated with a 2.5% higher mortality rate so
therapy-induced hypoglycaemia must be
avoided. ‘Why is it so dangerous?’ asked
Prof Schmidt. ‘It has pro-arrhythmic effects,
is associated with cognitive dysfunction
and delayed recovery in the elderly and is
both pro-thrombotic and pro-inflammatory.
In addition it causes increased anxiety in
patients, which in turn has a negative impact
on compliance.’ So control needs to be
both stringent and safe from the time of
diagnosis.
‘In 2013, when managing diabetes, we
need to avoid hypoglycaemia, especially in
those with cardiovascular risk, avoid weight
gain, reconstitute beta-cell function and
stop their loss. Is GLP-1 incretin therapy
an option?’ Prof Schmidt feels strongly that
it is.
‘GLP-1 normalises glucose levels in
poorly controlled patients, without causing
hypoglycaemia. Liraglutide improves first-
phase insulin secretion and maximal beta-
cell insulin capacity. Importantly, it does
not induce insulin secretion when glucose
levels are low. Used in combination with
metformin, the risk of hypoglycaemia is
low, comparable with that of placebo. It also
improves biomarkers of CVD risk, notably
reducing systolic blood pressure.’
Liraglutide therefore has a favourable
impact on the composite endpoint of
optimal HbA
1c
concentration, weight loss
and hypoglycaemia. ‘It shows great promise
in helping us get our patients to their
individualised HbA1c targets early, without
weight gain and hypoglycaemia, while
preserving beta-cell function’, Prof Schmidt
concluded.
P Wagenaar
