CARDIOVASCULAR JOURNAL OF AFRICA • Vol 23, No 5, June 2012
300
AFRICA
The role of aspirin in cardiovascular disease prevention
Prof Gordon T McInnes, University of
Glasgow, Scotland
Acetylsalicylic acid (aspirin) may have
been around for over 100 years, but
this ‘cheap and cheerful’ agent continues
to surprise with new indications for its
use. Prof Gordon McInnes feels that
this ‘old drug with new tricks’ has an
important ongoing role to play in both
the primary and secondary prevention of
cardiovascular disease (CVD). He was
speaking at a meeting hosted by Bayer
Healthcare in Johannesburg in May.
‘Aspirin was developed in 1897 and is
still going strong, with new indications
for its use continuing to appear’, he said.
‘We think we’re civilised, but we’re
doing a lot of things wrong and driving
ourselves to an early grave’, he warned.
As the developing world, including South
Africa, adopts Westernised lifestyles,
the tsunami of CVD previously seen in
Europe and North America is sweeping
through Asia and Africa, with 80% of
cases now seen in low- and middle-
income countries.
CVD accounts for 30% of all deaths,
12 million worldwide per year. ‘It’s the
number one killer on the planet. Over and
above that, there are 20 million survivors
of a stroke or myocardial infarction (MI)
each year, which makes it important to
look at preventing subsequent events.
Aspirin has a role to play in both primary
and secondary prevention.’
All forms of vascular disease have
the same underlying process and central
to this is the role of platelets – their
adhesion, activation and aggregation.
Antiplatelet treatments such as aspirin are
therefore very important.
Secondary prevention
In the secondary prevention of CVD,
aspirin’s role is clear and straightforward.
According to the Antithrombotic
Trialists’ Collaboration study published
in the
Lancet
in 2009,
1
it reduces the risk
of any vascular event by 19%, non-fatal
MI by 31%, stroke by 19% and vascular
mortality by 9%. ‘So there are benefits
across the board!’
When it comes to acute coronary
syndrome, aspirin’s benefits have been
shown in 15 trials. It prevents 30 serious
vascular events per 1 000 patients per
week, with the low risk of only one major
bleed per 1 000 patients per year. ‘There
is some debate around how long it should
be taken for, but much of the evidence
suggests that once you initiate, you should
continue for life.’ While it can be and
often is used in combination with other
treatments, it remains the foundation of
any antiplatelet approach.
Turning to aspirin’s longer-term use
post MI and in chronic stable angina,
Prof McInnes noted that there was good
evidence of benefit. ‘Twelve trials have
shown that post MI, it prevents 36 serious
vascular events per 100 patients per two
years, while 55 trials have shown that in
coronary heart disease (CHD) with no
MI, there is a 37% reduction in serious
vascular events. Seven trials have shown
benefit in acute ischaemic stroke, with
nine serious vascular events prevented
per 1 000 patients per three weeks. The
early introduction of aspirin is therefore
recommended.’
‘The evidence for more intensive
therapy with additional agents is weak,
but we’re still awaiting the results of
ongoing trials in this regard. Twenty-one
trials also support the use of maintenance
aspirin in transient ischaemic attack and
ischaemic stroke.’
Not all the news is good, though. Prof
McInnes feels that there is, sadly, not
much benefit in atrial fibrillation, with
only one trial having shown positive
results. ‘Aspirin’s days as a protective
agent in this setting are gone, especially
with the advent of the newer agents that
are safer than warfarin.’
However, the news is good where
peripheral vascular disease is concerned.
Aspirin is associated with a 23%
reduction in serious vascular events and,
importantly, improved symptoms
Primary prevention
In this context, the evidence is less clear
cut than that for secondary prevention.
‘The most recent meta-analysis published
by Berger
et al.
2
showed a 50% or higher
risk of major bleeding with only modest
risk reduction in MI, stroke, CV death
and all death. There is also conflicting
evidence around the use of aspirin for
primary CVD prevention in diabetics.
‘However, the POPADAD
3
and JPAD
4
trials, which produced these conflicting
findings, were underpowered and
imprecise, so clinical benefit cannot be
ruled out.’
Another reason for the conflicting
evidence in primary prevention is the
phenomenon of aspirin resistance. ‘A
meta-analysis by Kraspoulos
et al.
,
5
showed that 28% of the CVD subjects
involved were resistant. This would dilute
apparent benefits and may be responsible
for the modest nature of the benefits seen
in primary prevention.’
There are also gender differences in
primary prevention in that aspirin appears
to reduce ischaemic stroke but not MI in
women. The picture may be reversed in
men.
Discontinuation of aspirin in patients
with a history of ischaemic events is
nonetheless associated with a major
increased risk of non-fatal MI or CHD
death within 30 days. ‘This is evidence
for continuation and suggests that patients
should never discontinue aspirin therapy
without careful consultation with medical
professionals’, Prof McInnes advised.
Other benefits
There has been some good news in recent
years, with high-quality data indicating
that aspirin reduces the risk of large
bowel cancer. A meta-analysis of 51
trials showed substantial reductions in
cancer death, incident cancer and spread
of cancer, suggesting that ‘an aspirin a
day keeps cancer away’. ‘A decreased
risk of type 2 diabetes may also be added
to the list of clinical benefits of aspirin’,
said Prof McInnes, ‘although these data
are somewhat less compelling.’
So what does all this mean for primary
prevention? Prof McInnes feels that
it is important to do an in-depth risk
assessment to guide decision making but
that in patients over 50 years, there is
indeed clear benefit that becomes even
more apparent as age increases, especially
when one factors in cancer.
‘The provision of aspirin in people
at increased vascular risk provides the
greatest benefit and has the lowest cost
by far of any preventive measures, apart
from smoking cessation’, he concluded.
‘After all these years, aspirin still hits the
target.’
Peter Wagenaar
1.
Antithrombotic trialists’ (ATT) collabora-
tion.
Lancet
2009;
373
: 1849–1860.
2.
Berger JS,
et al
.
Am Heart J
2011;
162
:
115–124.
3.
Belch J,
et al
.
Br Med J
2008;
337
: 1030–
1034.
4.
Ogawa H,
et al
.
J Am Med Assoc
2008;
300
:
2134–2141.
5.
Krasopoulos G,
et al
.
Br Med J
2008;
336
:
195–198.
