Background: The progression of cerebral atherosclerosis increases the risk of stroke and vascular events. Given the known benefits of statins in retarding coronary and carotid atherosclerosis progression, we studied the effects of statins on asymptomatic middle cerebral artery (MCA) stenosis progression. Methods: We conducted a randomized, double-blind, placebo-controlled study to evaluate the effects of simvastatin on the progression of MCA stenosis among stroke-free individuals who had mild to moderately elevated LDL cholesterol (3.0–5.0 mmol/l). Two hundred and twenty-seven subjects were randomized to either placebo (n = 114) or simvastatin 20 mg daily (n = 113). The severity of MCA stenosis at baseline and at the end of the study was graded by MRA into normal, minimal (<10%), mild (10–49%), moderate (50–90%) and severe (>90%). The primary outcome was the change in grading of MCA stenosis over 2 years. Results: At the end of the study, the LDL cholesterol level decreased by 1.43 and 0.12 mmol/l for the active and placebo groups, respectively (p < 0.001). There was no significant difference in the proportion of patients having stable, progressive and regressive MCA stenosis between the placebo (72, 22 and 6%) and active groups (78.6, 15.5 and 5.8%). The all-cause mortality was significantly lower in the active group (n = 0) relative to the placebo group (n = 7, p = 0.014). Any clinical events were also lower in the active group (n = 5) than in the placebo group (n = 13, p = 0.052). Conclusions: Simvastatin 20 mg daily had no apparent effect upon the evolution of asymptomatic MCA stenosis over 2 years.

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