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Stroke and the pharmaceutical industry
Recent developments with established medicine
Medicines that reduce plaque formation
A major risk factor for plaque formation is high blood cholesterol,
which contributes towards the build-up of plaque in the blood
vessels. This can then lead to thrombus formation in the arteries
feeding the brain or the possibility of an embolism (‘wandering’
clot). Hence, medicines that reduce or stabilise plaque, can
be beneficial especially in preventing a second stroke. One
class in particular, the statins, is emerging as a significant
player in the battle against plaque. Pravastatin (Bristol-Myers
Squibb) has been shown to reduce the risk of stroke in people
who have raised cholesterol levels and have had a heart attack.
Trials with simvastatin (Merck Sharp & Dohme) also indicate
useful effects and further large-scale trials are in progress.
These compounds work by blocking a main step in the pathway
used by the body to synthesise cholesterol and hence reduce
the levels in circulation.
Two major clinical trials with pravastatin (known as the
CARE and LIPID Trials) in people who had experienced a first
heart attack or had heart disease (both stroke risk factors)
showed a reduction in the risk of stroke. In the first, pravastatin
reduced the risk of stroke by 31 per cent and TIAs by 27 per
cent compared with placebo. In the second, the benefits became
so apparent (19 per cent reduction in stroke) that the trial
was stopped early, because the investigators felt it unethical
to deny the people on placebo the benefits of the pravastatin.
In both studies, the benefits observed were in addition to
aspirin and high blood pressure medicines. The statin reduced
the blood levels of different forms of cholesterol by 20-32
per cent and fats by 14 per cent. Bristol Myers Squibb is
now conducting another trial (the PROSPER Trial) specifically
in the elderly (70-82 years of age). This will investigate
all types of cardiovascular disease, including stroke, but
the results will not be available for some time.
Simvastatin has been studied in a further large group of
people followed over 5.4 years. The results indicated a reduction
in TIAs by 28 per cent. Analyses of several other trials also
showed that simvastatin reduced what are called bruits in
the carotid artery by 48 per cent – a bruit is an abnormal
sound that the doctor can hear with a stethoscope as blood
squeezes past a developing plaque. It is important to be aware,
however, that while there is an established link between blood
cholesterol levels and heart disease, no such link has yet
been proved between cholesterol and stroke. It has been suggested
that the beneficial effects of pravastatin and simvastatin
arise from the effect they have on the speed of plaque development
and on plaque stability, i.e. preventing plaques from shedding
emboli.
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