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An overview of trials of cholesterol lowering and risk of stroke
P R Hebert1, J M Gaziano, C H Hennekens
1Division of Preventive Medicine, Brigham & Women's Hospital, Boston, Mass.
Insights
Cholesterol lowering treatments did not significantly reduce the risk of stroke in a large overview of trials. Further research is needed to clarify potential benefits or harms of lipid-lowering on stroke and overall mortality.
Area of Science:
- Cardiovascular Medicine
- Neurology
- Clinical Trials
Background:
- Blood cholesterol levels are established predictors of coronary heart disease.
- The association between cholesterol levels and stroke risk, particularly ischemic stroke, remains uncertain despite some observational evidence.
- Atherogenic processes underlie both coronary heart disease and ischemic stroke, making the link plausible.
Purpose of the Study:
- To investigate the efficacy of lipid-lowering interventions in reducing stroke risk.
- To synthesize evidence from randomized trials on the impact of cholesterol reduction on stroke outcomes.
Main Methods:
- An overview of randomized controlled trials was conducted.
- The analysis included over 36,000 individuals receiving lipid-lowering treatment compared to control groups.
- Data on fatal and nonfatal stroke events were analyzed.
Main Results:
- Lipid-lowering treatments achieved mean cholesterol reductions of 6% to 23%.
- No statistically significant reduction in the risk of all strokes (fatal plus nonfatal) was observed (relative risk, 1.0).
- The risk of fatal stroke also showed no significant change (relative risk, 1.1).
Conclusions:
- Current evidence suggests that cholesterol lowering may not offer significant benefits for stroke risk.
- The wide confidence intervals for fatal stroke indicate that small protective or harmful effects cannot be definitively ruled out.
- Further large-scale trials are recommended to assess total mortality and nonvascular causes of death associated with lipid-lowering therapies.
Background:
While blood cholesterol level predicts coronary heart disease, whether there is any association with the risk of stroke is unclear. Some, but not all, observational studies suggest that cholesterol level predicts risk of stroke, particularly ischemic stroke. This hypothesis is attractive because ischemic events constitute the vast majority of all strokes and, like coronary heart disease, involve atherogenic processes.
Methods:
To investigate whether lipid lowering reduces the risk of stroke, we performed an overview of randomized trials that included more than 36,000 individuals.
Results:
The mean reduction in cholesterol level in the treated as compared with the control subjects ranged from 6% to 23%. Those assigned to treatment experienced no significant reduction in all (fatal plus nonfatal) stroke (relative risk, 1.0; 95% confidence interval, 0.8 to 1.2) or fatal stroke (1.1; 0.8 to 1.6).
Conclusions:
The confidence interval for fatal stroke is wide, and alternative hypotheses, including either a small protective or harmful effect, cannot be excluded; however, the point estimates are compatible with no benefit of cholesterol lowering on the risk of stroke. Additional large-scale randomized trials assessing total mortality would more definitively address any benefits on stroke, as well as any excess nonvascular causes of mortality, for which risks of cholesterol lowering also remain uncertain.