Cholesterol-Lowering Interventions and Stroke Insights From a Meta-Analysis of Randomized Controlled Trials

Objectives This meta-analysis was performed to determine the effects of various cholesterol-lowering treatments on the risk of stroke and its relationship with the extent of cholesterol lowering. Background Statins reduce the incidence of stroke, and it has been proposed that such effect is independent of cholesterol lowering and is explained by alternative mechanisms. Methods We performed a meta-analysis of randomized trials of cholesterol-lowering treatments in cardiovascular disease reporting on stroke, involving 266,973 patients investigated and a cumulative 946,582 person-years of exposure, and a meta-regression analysis of the extent of stroke reduction as a function of changes in total cholesterol. Results The odds ratio (OR) for the incidence of stroke in actively treated groups versus controls was 0.88 (95% confidence interval: 0.83 to 0.94, p < 0.001). No treatment affected fatal strokes. Whereas statins decreased the risk of total stroke significantly (OR: 0.85, 95% confidence interval: 0.78 to 0.92; p < 0.001), the benefit of non-statin interventions was smaller and not statistically significant (diet OR: 0.92, fibrates OR: 0.98, other treatments OR: 0.81). We found a significant relationship between percent reduction of total (and low-density lipoprotein) cholesterol and percent reduction of total strokes (p = 0.0017), with each 1% reduction of total cholesterol predicting a 0.8% relative risk reduction of stroke. We found no significant association between stroke reduction and changes of high-density lipoprotein cholesterol levels, and inconsistent associations with reduction of triglycerides. Conclusions Among cholesterol-lowering treatments, statins are the most effective at decreasing the risk of total stroke, but their benefit is proportional to the percent reduction of total cholesterol and low-density lipoprotein cholesterol. No lipid-lowering intervention was associated with a reduction of fatal stroke. (J Am Coll Cardiol 2010; 55: 198-211) (C) 2010 by the American College of Cardiology Foundation