Hypercholesterolemia, lipid-lowering agents, and the risk for brain infarction

Clinical trials in the 1990s using HMG-CoA reductase inhibitors (statins) showed that cholesterol-lowering treatment significantly reduces cardiovascular events including strokes in the primary and secondary prevention of myocardial infarction (MI). Paradoxically, the link between serum cholesterol level and the incidence of stroke remains to be fully established. This is largely due to conflicting evidence from a series of observational cohort studies and a suggestion that lowering serum cholesterol increased the risk for hemorrhagic stroke. These findings have tended to influence the treatment of stroke, despite alternative interpretations for the failure of these studies to find a clear association between cholesterol levels and stroke. The statin trials present a strong argument for a reappraisal of the link between cholesterol and stroke. Three meta-analyses have all shown a relative risk reduction in stroke of 12 to 48% in patients with coronary heart disease (CHD) after MI. There was no statistically significant increase in hemorrhagic stroke. Recently, gemfibrozil has also been shown to reduce the relative risk for stroke (25%), which contradicts the findings of previous fibrate trials. It is becoming clear that the clinical action of many cholesterol-lowering drugs is the result of pleiotropic/antiatherogenic effects rather than simply a reduction in cholesterol. There is also evidence that these agents exert direct effects that promote atherosclerotic plaque stability. After these observations, it is now generally accepted that lipid-lowering treatment should be considered in all stroke patients with a history of CHD/MI. However, for the remaining patients with ischemic stroke, there is no proven therapeutic approach, and several large randomized, placebo-controlled trials are under way or planned for this indication.