Effects of cholesterol-lowering with simvastatin on stroke and other major vascular events in 20 536 people with cerebrovascular disease or other high-risk conditions

Lower blood cholesterol concentrations have consistently been found to be strongly associated with lower risks of coronary disease but not with lower risks of stroke. Despite this observation, previous randomised trials had indicated that cholesterol-lowering statin therapy reduces the risk of stroke, but large-scale prospective confirmation has been needed. 3280 adults with cerebrovascular disease, and an additional 17256 with other occlusive arterial disease or diabetes, were randomly allocated 40 mg simvastatin daily or matching placebo. Subgroup analyses were prespecified of first “major vascular event” (ie, non-fatal myocardial infarction or coronary death, stroke of any type, or any revascularisation procedure) in prior disease subcategories. Subsidiary outcomes included any stroke, and stroke subtype. Comparisons are of all simvastatin-allocated versus all placebo-allocated participants (ie, “intention-to-treat”), which yielded an average difference in LDL cholesterol of 1·0 mmol/L (39 mg/dL) during the 5-year treatment period. Overall, there was a highly significant 25% (95% CI 15–34) proportional reduction in the first event rate for stroke (444 [4·3%] simvastatin vs 585 [5·7%] placebo; p