CARDIOVASCULAR JOURNAL OF AFRICA • Vol 24, No 3, April 2013
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AFRICA
stroke of arterial origin because it is effective and inexpensive.
Aspirin reduces recurrent strokes rather than limiting the
neurological consequence of a stroke.
12
Two large trials evaluated aspirin for the treatment of acute
ischaemic stroke.
31,32
The Chinese Acute Stroke trial (CAST)
and the International Stroke trial (IST) randomised just over 40
000 patients with acute ischaemic stroke. In conjunction, these
studies concluded that aspirin given within 48 hours of stroke
produces a modest but definite benefit with about 10 fewer
deaths or recurrent strokes per 1 000 in the first few weeks. Oral
aspirin (150–300 mg loading dose) given within 48 hours after
ischaemic stroke is recommended. However, aspirin or other
antithrombotic therapy should not be initiated within 24 hours if
thrombolytic therapy is given.
4
Dipyridamole plus aspirin, or clopidogrel alone, is more
superior to aspirin alone in secondary prevention of strokes
and other vascular events and their overall safety profiles
are similar.
33,34
However, a considerable proportion of patients
discontinue dipyridamole therapy because of headache,
35
and
clopidogrel is more expensive than aspirin. Clopidogrel in
conjunction with aspirin is not more effective than clopidogrel
alone in preventing ischaemic strokes and other vascular events.
Furthermore, this combination also increases the risk of major
bleeding.
36
Although the AHA guidelines do not recommend clopidogrel
or dipyramidole either alone or in conjunction with aspirin for the
treatment of acute ischaemic stroke, a recent systematic review,
which assessed the clinical effectiveness and cost effectiveness
of the above three agents, used either alone or in combination,
concluded that for patients with ischaemic stroke or TIA,
modified-release dipyridamole + aspirin, followed by aspirin
alone, followed by clopidogrel, appears to be a cost-effective
approach to the prevention of future occlusive vascular events.
37
Intravenous glycoprotein IIb/IIIa inhibitors such as abciximab
are currently not recommended for use in acute ischaemic stroke
until more research is available.
12
Newer antithrombotic agents
that have shown efficacy in acute coronary syndromes, such
as thienopyridine and prasugrel, and the non-thienopyridine,
ticagrelor (a reversibleADP receptor antagonist) may be promising
potential treatments for acute TIA and ischaemic stroke.
28
Anticoagulants
Data suggest that early anticoagulation with heparin or the
low-molecular weight heparins/danaparoid does not lower the
risk of early recurrent strokes nor does it halt neurological
worsening. It also increases the risk of bleeding in the brain or
other parts of the body. Hence it is not recommended for use in
acute ischaemic strokes and should certainly not be given within
24 hours of thrombolytic therapy.
12
Warfarin is universally used as an antithrombotic therapy for
patients with TIA or ischaemic strokes of cardiac origin. Warfarin
has been shown to reduce the risk of recurrent stroke or systemic
embolism by about 61% in atrial fibrillation (AF) patients
with recent TIA or ischaemic stroke.
38
However warfarin does
increase the risk of major extracranial haemorrhage. According
to the South African stroke guidelines, dose-adjusted warfarin
is recommended for patients with cardio-embolic ischaemic
stroke or TIA associated with intermittent or persistent atrial
fibrillation.
4
Newer oral anticoagulants such as dabigatran, apixabin and
rivaroxaban have emerged and trials on these drugs in stroke
prevention for patients in AF appear promising. Recently, three
large phase III randomised, controlled trials, the Randomized
Evaluation of Long-TermAnticoagulationTherapy (RE-LY) trial,
the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition
Compared With Vitamin K Antagonism for Prevention of Stroke
and EmbolismTrial in Atrial Fibrillation (ROCKET AF), and the
Apixaban for Reduction of Stroke and Other Thromboembolic
Events in Atrial Fibrillation (ARISTOTLE) trial have shown that
dabigatran, rivaroxaban and apixabin are each more efficacious
than warfarin for preventing strokes in patients with AF, with
lower rates of intracranial bleeding.
39-41
Other advantages of these
anticoagulants over warfarin are that they can be used in fixed
doses and regular monitoring of anticoagulation intensity is not
necessary.
42
The FDA has approved dabigatran and rivaroxaban for stroke
reduction in people with non-valvular atrial fibrillation.
43
FDA
approval for apixabin is pending. Three studies have compared
these three oral anticoagulants for stroke prevention in AF
patients.
44-46
Apixaban was shown to be as effective as dabigatran
but rivaroxaban was less effective than dabigatran.
44
Apixaban
was associated with less major bleeding than dabigatran or
rivaroxaban.
44
Dabigatran is more cost effective than rivaroxaban
in terms of acute care and long-term follow up costs, as well as
accrual of quality-adjusted life years.
45
Apixaban is associated
with less major and gastrointestinal bleeding than dabigatran and
rivaroxaban.
46
Randomised trials comparing the three drugs are
required to confirm these findings.
Apixabin was also directly compared to aspirin in the
Apixaban Versus Acetylsalicylic Acid to prevent Strokes
(AVERROES) trial and shown to be more effective in reducing
strokes compared to aspirin in AF patients who have had
previous strokes or TIAs and who are unsuitable for or unwilling
to take a vitamin K agonist.
47
Treatment of dyslipidaemia
Dyslipidaemia is a major risk factor for coronary heart disease but
its role in ischaemic stroke is not clear. It is however associated
with atherosclerosis, which causes strokes.
4
A meta-analysis of
90 000 patients suggested that larger low-density lipoprotein
cholesterol (LDL-C) reductions better reduce the risk of stroke.
48
In five placebo-controlled studies with more than 40 000
patients with coronary heart disease, HMG-CoA reductase
inhibitors (statins) reduced the risk of stroke by 19–50%.
49
Of
all the statins, atorvastatin is the most favourable.
49
Simvastatin
reduced major vascular event by 20%. AHA guidelines
recommend using a statin to reduce the risk of recurrent stroke
in patients with evidence of atherosclerosis, an LDL-C level
>
100 mg/dl, and those who are without known coronary heart
disease.
50
Maximum benefit is attained with a reduction of the
LDL-C level by at least 50% or below 70 mg/dl.
Other medications used to treat dyslipidaemia include
niacin, fibrates and cholesterol-absorption inhibitors. Niacin
and gemfibrozil are recommended (class 2b) for use in patients
with ischaemic stroke or TIA with low high-density lipoprotein
cholesterol (HDL-C.) levels. Lipid-lowering therapy is associated
with delayed cardiovascular events and prolonged survival in
patients with homozygous familial hypercholesterolaemia.
51
