Cardiology
Drug-eluting stents in interventional cardiology: benefits and risks
Drug-eluting stents have had a substantial impact on the treatment of
coronary artery disease with more than a million of these devices
inserted in coronary patients in the United States alone each year.
Although they do appear to be a safer option than the older bare-metal
stents, they are not used entirely without risk. Sarah Hamida Javaid
reports.
Coronary artery disease is one
of the leading causes of death
worldwide. In 2004 an estimated
17.4 million people died
from the disease, according to
the World Health Organisation,
representing 29% of all global
deaths that year. Accurate
figures for the Middle East
region are more difficult to
come by, however according to
the WHO the Eastern
Mediterranean Region is
facing a growing epidemic of
cardiovascular diseases provoked
by an ageing population and
socioeconomic changes.
For years cardiologists have
tackled this disease with
medication and surgery.
However, the primary antidote
for this deadly disease is risk
factor modification – that is
eating the correct diet,
ensuring adequate physical
activity and stopping smoking.
Yet, the reality remains that
even after lifestyle changes,
the disease can still progress
with a downward spiral, necessitating
intervention.
To date percutaneous coronary
intervention (PCI) has
proven to be one of the most
effective ways to improve lifethreatening
cardiovascular
conditions, such as acute
myocardial infarction, and is
highly effective in relieving
symptoms, especially if
medications fail.
Over the past five or six
years the use of drug-eluting stents (DES) in PCI has
proved to be one of the most
beneficial breakthroughs in
this field of medicine, as they
significantly reduce the risk of
restenosis of coronary arteries,
one of the major drawbacks of
the older bare-metal stents,
which had been used regularly
in PCI prior to the development
of the drug-eluting stent.
Currently, in the United States
alone, more than 1,000,000
procedures using DES are
carried out each year.
Knowledge
At the 2009 European Society
of Cardiology Congress in
Barcelona several speakers
highlighted the fact that
research on DES is flourishing,
indicating a major interest in
its prominent and integral
place in interventional cardiology.
Cardiology conferences in
the Middle East have also
played an important role in the
dissemination of knowledge
about the benefits of DES.
Dr Omar Hallak, chief of the
Interventional Cardiology
Department at the American
Hospital in Dubai, chaired a
conference in 2008 in the
United Arab Emirates that
introduced the latest advances
in cardiology, along with the
new generation of DES.
“There have been multiple
cardiology meetings in the
United Arab Emirates in recent
years,” says Dr Hallak. “These
conferences provide a forum in
which experts in the field from
around the world bring their
knowledge and expertise and
share them with local cardiologists.
This is invaluable in
improving the quality of cardiac
care [in the region].”
Dr Joseph Malouf, a
consultant cardiologist at
Mayo Clinic, acknowledges
the widespread use of the
device in the Middle East and
points out that its use is on the
rise concomitant with the
increase in the prevalence of
coronary artery disease in the
region.
Restenosis
DES significantly reduce
restenosis in arteries
compared to bare-metal
stents, explains Dr Malouf.
However, aside from reducing
the risk of restenosis, there are
no significant differences to
date in terms of outcome.
Moreover, he says there is an
increased risk of stent thrombosis
with DES, albeit this risk
is very low. Unlike the baremetal
stent, the drug-eluting
stent is not endothelialized,
thus exposing the surface of
the stent to blood elements
and increasing the risk of
thrombus formation. For this
reason, the use of anti-platelet
drugs, plavix and aspirin, for
an extended period of time
(up to one year or more) after
deployment of DES is very
important. This is in contrast
to bare-metal stents in which
anti-platelet drugs are typically
given for one month.
The main indications for stent deployment in coronary
artery disease are to treat
acute myocardial infarction
and provide symptom relief,
explains Dr Malouf. In acute
myocardial infarction stent
deployment is superior to
thrombolysis provided it is
done in a timely manner
because of the limited
window of opportunity available
to restore heart muscle
function after acute myocardial
infarction.
Diabetes
Diabetes is epidemic and
prevalence continues to
increase in the Middle East.
One of the main concerns with
this condition is the development
of serious secondary
complications, such as coronary
artery disease1.
Dr Hallak explains that DES
are commonly used in patients
with diabetes. It has also been
shown that restenosis is lower
with DES compared to baremetal
stents in patients with
diabetes.1
However, Dr Malouf says
that whether or not stents are
as good as surgery is an issue to
consider in patients with
diabetes. The question arises
that if surgery improves
survival do stents do the same?
In the past, stents have not been considered to be as effective
as surgery, but Dr Malouf
points out that recent studies,
which suggest that stents
maybe as effective as surgery,
are changing this perception.
Symptom relief
With more than a million
drug-eluting stent insertions
performed in the US alone
each year, it can be asked
whether they are being overused?
Dr Malouf, thinks this
may be the case and says, in his
opinion, this procedure is
being over-deployed.
He says that there are indications
and situations necessitating
the utilisation of stents,
such as acute myocardial
infarction, but in patients with
chronic stable angina, medications
and intense risk factor
control have proved to be as
good, if not superior, to stent
deployment, as shown by the
COURAGE Trial2.
Dr Malouf emphasises that
stents are mainly of use to
relieve symptoms and are not
indicated in patients with
chronic coronary artery disease
without symptoms or evidence
of myocardial ischemia on
stress testing.
The jury is still out on
whether stents improve
survival or reduce the risk of
myocardial infarction in
patients with chronic coronary
artery disease.
Thrombosis
One of the key debates
surrounding stents is whether
the DES is actually more beneficial
than the bare-metal
stent, as although the DES
have been shown to have a
lower incidence of restenosis
compared to bare-metal stents,
some studies have shown that
the DES have a higher incidence
of late stent thrombosis.
A presentation at the 2009
European Society of
Cardiology Congress in
Barcelona highlighted a study ²
(a five year follow-up of all
patients treated with DES
compared to bare-metal stents
in Sweden, based on the
SCAAR registry) that shows
there is no increased risk associated
with DES, but late stent
thrombosis still remains a
serious concern.
Dr Hallak, who is experienced
in the implantation of
DES, says that acute stent
thrombosis is most commonly
due to technical problems such
as incomplete apposition of the stent, incomplete expansion of
the stent, edge dissection and
multiple stent deployment.
The cause for late stent thrombosis
is usually attributed to
not taking the dual antiplatelet
drugs, plavix and
aspirin, daily. In the event of
thrombus formation the
problem is localised to the site
of stent deployment, and
thrombosis is not likely to
increase through progression to
a different vessel.
Various hypotheses to
explain the development of stent thrombosis, a critical
concern with DES, are being
investigated. One such
hypothesis is that hypersensitivity
reactions causes thrombosis
in diabetic patients with
DES. Dr Hallak says that
there are several other theories
for late stent thrombosis
development, such as the
resistance to anti-platelet
medication.
Patients are expected to use
anti-platelet medication for
bare metal stents for one to
three months, and for DES for
nine to twelve months.
Recommendations may be
given for use of anti-platelet
drugs for an indefinite duration
especially in patients at
high risk for stent thrombosis,
such as those with multiple
stents and complex lesions.
Thrombosis carries a 50%
risk of myocardial infarction
and death according to Dr Hallak. It is for this reason that
DES remain under intense
scrutiny. PCI, including DES
and bare metal stents, do not
reduce the rate of major
adverse cardiac events, says Dr
Hallak, emphasising that the
main purpose of DES is to
improve the quality of life and
alleviate symptoms. He adds
that the main treatment
proven to decrease major
adverse cardiac events is risk
modification.
Economy
The cost associated with use of
DES is still very high. The drugeluting
stent world market is
estimated to be worth US$6
billion3, making it one of the biggest markets in medical technology.
When released for the
first time, the cost of DES was
about five times that of bare
metal stents.4 Moreover, PCI is
still very expensive.
Cost-effectiveness analyses
aim to explain the divide
between the costs and benefits
of DES. Funding by the industry
also has a significant influence
over the use of DES, as direct
sponsorship from manufacturers
of DES encourages more widespread
use.3 Dr
Hallak says that
cardiologists hope that DES will
become more affordable so that
more patients can benefit from
this procedure.
Biodegradable
The latest research has
focused on a biodegradable
polymer coating for the drugeluting
stent. Dr Hallak
explains that the first generation
of DES did carry about a
7% risk of instant restenosis,
in the second generation the
design of the struts was
improved, in the third generation
the polymer and
medications used to coat the
DES became more advanced,
and the latest, or the fourth
generation, stent has become
bioabsorbable. These
improvements significantly
reduce the chance of
restenosis and almost eliminate
the risk of late stent
thrombosis.
With risk reduction at the
centre of research, DES looks
set to remain an integral part
of interventional cardiology for
years to come.
References
1. Carlsson J, Frobet O, James
SK, et al. “Safety and efficacy
of drug-eluting vs. bare metal
stents in patients with
diabetes mellitus: long-term
of follow-up in the Swedish
Coronary Angiography
and Angioplasty Registry
(SCAAR)”. European Heart
Journal 2009.
2. Bates ER, Berman DS, Boden WE, et al. “Optimal
medical therapy with or
without PCI for stable coronary
disease”. The New
England Journal of Medicine
2007.
3. Brophy JM, Dendukuri N,
Ligthart S, et al. “The costeffectiveness
of drugeluting
stents: a systematic
review”. CMAJ 2007;
176(2):199-205.
4. Crossman DC, Cumberland
DC, Gunn J, et al. “Drugeluting stents: maximising
benefit and minimising cost”.
Heart 2003; 89(2):127-131. 
Date
of upload: 26th Jan 2010
