Atherothrombosis results from direct interaction between the
atherosclerotic plaque and arterial
thrombosis, and underlies most forms of
cardiovascular disease (CVD). The pathophysiology of
atherosclerosis is now recognised to involve endothelial dysfunction and
dyslipidemia with
cholesterol accumulation, as well as critical immuno-inflammatory and apoptotic dimensions. Erosion or
rupture of a vulnerable,
lipid-rich, inflammatory
atherosclerotic plaque triggers the formation of a platelet-rich
thrombus that may partially or completely occlude the artery, with resultant clinical scenarios including stable and
unstable angina, acute
myocardial infarction (MI) and
ischaemic stroke. Insight into the pathophysiology of
atherothrombosis indicates that an integrated risk factor approach, focusing particularly on management of dyslipidaemia (with a
statin) and
thrombosis (with
aspirin), may constitute an optimal therapeutic approach. Both agents have established roles in
secondary prevention.
Statin action on atherogenic
lipoproteins mediates plaque stabilisation, modification of plaque morphology and attenuation of
inflammation, and may lead to plaque regression, while
aspirin reduces platelet activation and aggregation, decreases release of inflammatory
cytokines at sites of
vascular injury and attenuates vasoconstriction. Given these complementary modes of action, this combination would be a logical choice for reducing atherothrombotic risk in patients with CVD. Meta-analysis of 5 major clinical studies has demonstrated that the combination of
pravastatin plus
aspirin was significantly more effective than either agent alone in reducing the relative risk of key cardiovascular endpoints including MI and
ischaemic stroke. This combination may therefore represent an important, cost-efficient therapeutic approach to reduction of cardiovascular risk and prevention of recurrent events in stable CVD.