Clinical Research
Lipid-Lowering and Stroke
Cholesterol-Lowering Interventions and Stroke: Insights From a Meta-Analysis of Randomized Controlled Trials

https://doi.org/10.1016/j.jacc.2009.07.062Get rights and content
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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 nonstatin 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.

Key Words

statins
HMG-CoA reductase inhibition
stroke
cholesterol
pleiotropic effects
neuroprotection

Abbreviations and Acronyms

CHD
coronary heart disease
CI
confidence interval
HDL-C
high-density lipoprotein cholesterol
LDL-C
low-density lipoprotein cholesterol
OR
odds ratio
RCT
randomized clinical trial
RR
relative risk
TC
total cholesterol

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