Recent clinical trials and meta-analyses of b-hydroxy-bmethylglutaryl coenzyme A (HMG-CoA)
reductase inhibitors (statins) have demonstrated a significant reduction in ischemic stroke
in patients with a history of coronary artery disease, both with and without elevations of
serum cholesterol. Recent data suggest that statins have other beneficial properties in
addition to the retardation of atherosclerosis. Asahi et al demonstred that Statins increased
eNOS and tPA mRNA levels but did not change mRNA levels of PAI-1 and that In eNOS knockout
mice, atorvastatin reduced the volume of ischemic tissue and improved neurologic outcomes
after arterial occlusion by blood clot emboli. In addition to their lipid-lowering effects,
it has been speculated that statins may also have beneficial effects on cerebral circulation
and brain parenchyma during ischaemic stroke and reperfusion. Aslanyan et al reported that
statin use was associated with reduced mortality at 1 month during the follow-up.
In patients with recent stroke or TIA and without known coronary heart disease, 80 mg of
atorvastatin per day reduced the overall incidence of strokes and of cardiovascular events,
despite a small increase in the incidence of hemorrhagic stroke period .
Recently the investigators group reported that lacunar strokes compared to nonlacunar ones
exhibited significantly lower plasma levels of TNF-α and IL1-β, P-selectin and ICAM-1 24-72 h
and 7-10 days after stroke onset (4). At extracranial arterial territories, inflammation
plays a crucial role mediating all the stages of the atherosclerosis process . Similarly,
thrombosis and defective fibrinolysis may also contribute to the progression of
atherosclerotic lesions . Interestingly, both mechanisms might have a relevant role in the
pathogenesis of intracranial large artery atherosclerosis and ischemic stroke Moreover our
group showed that Patients with cardioembolic and atherothrombotic stroke subtypes showed
significantly higher median plasma levels of TNF-α, IL-6, IL-1β whereas the lacunar subtype
showed significantly lower median plasma levels of TNF-α, IL-6 and IL-1β and that
immunoinflammatory marker plasma levels are significantly related to ischemic lesion volume.
A meta-analysis showed that statins may possess antithrombotic property because these drugs
were reported to reduce periprocedural infarction in patients undergoing percutaneous
coronary intervention .
This clinical benefit was detected after median, 0.5 days of treatment with statins
(indicating that statins could potentially exert an antithrombotic effect even earlier than
supposed from pharmacological studies.
Violi et al recently showed the first evidence that atorvastatin acutely and simultaneously
decreases oxidative stress and platelet activation by directly inhibiting platelet Nox2 and
ultimately platelet isoprostanes and thromboxane A2 so providinf a rationale for the use of
statins to prevent or modulate coronary thrombosis.
Whereas recent data suggest that inflammatory reactions are involved in the pathogenesis and
progression of cerebral ischaemia , no study has evaluated effects of atorvastatin 80 mg/day
after a recent stroke on stroke outcome and on immunoinflammatory markers so to evaluate
acute antithrombotic and anti-inflammatory effects of atorvastatin also in acute
cerebrovascular event setting.
On this basis the primary objective of the study was to evaluate the separate effects of
atorvastatin in vivo on immunoinflammatory markers and on stroke prognosis in patients with
recent acute ischemic stroke classified as atherothrombotic.