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Intensive statin therapy after stroke or transient ischemic attack: a SPARCLing success?

Anyone aware of the conflicting data regarding the importance of circulating cholesterol in stroke will welcome the results of the Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) trial.1 Unlike with coronary heart disease, epidemiological studies often failed to demonstrate an association between elevated cholesterol levels and stroke incidence.2 However, many studies did not take into account the distinct underlying pathophysiological mechanisms of stroke and instead examined conflated end points such as a combination of ischemic and hemorrhagic stroke, or total ischemic stroke without subtyping, and others did not evaluate cholesterol subfractions. In contrast, epidemiological studies that carefully distinguished ischemic and hemorrhagic strokes generally found both a modest association of elevated cholesterol with increased risk of ischemic events and of low cholesterol with an increased risk of intracerebral hemorrhage.3

HMG-CoA reductase inhibitors or “statins,” which inhibit the synthesis of cholesterol that contributes to atheroma development and progression, have been shown to reduce the risk of first stroke in patients with established coronary heart disease, diabetes, or multiple cardiovascular risk factors.4 Indeed, as our cardiology colleagues kept finding the benefit of lower and lower cholesterol targets for reducing the risk of coronary heart disease events,5 the jury remained out as to what role, if any, that statins played in stroke patients without established coronary heart disease.

Subset analyses of prior clinical trials had suggested, but not definitely proved, a benefit of statin therapy in patients with prior strokes. A retrospective subset analysis of 3280 subjects with a remote (mean 4.3 years) history of symptomatic ischemic cerebrovascular disease enrolled in the Heart Protection Study (HPS) showed that simvastatin therapy yield a 20% reduction in major vascular events (0.80, 0.71 to 0.92).6 This benefit was driven by a reduction in myocardial infarction and vascular death end …