Statins in stroke prevention and carotid atherosclerosis: systematic review and up-to-date meta-analysis.
Previously published meta-analyses exploring the effect of statins on stroke incidence included 20,000 patients and found a 2% to 30% risk reduction. It is not clear whether this is attributable to low-density lipoprotein-cholesterol (LDL-C) reduction. Statin trials have now included >90,000 patients. We have determined the effect of statins and LDL-C reduction on stroke prevention. We performed a systematic review and meta-analysis of all randomized trials testing statin drugs published before August 2003. The trials were identified using a computerized PubMed search. We analyzed separately statin effect on incident strokes and on carotid intima-media thickness (IMT) according to LDL-C reduction. The relative risk reduction for stroke was 21% (odds ratio [OR], 0.79 [0.73 to 0.85]), with no heterogeneity between trials. Fatal strokes were reduced but not significantly: by 9% (OR, 0.91 [0.76 to 1.10]). There was no increase in hemorrhagic strokes (OR, 0.90 [0.65 to 1.22]). Statin size effect was closely associated with LDL-C reduction. Each 10% reduction in LDL-C was estimated to reduce the risk of all strokes by 15.6% (95% CI, 6.7 to 23.6) and carotid IMT by 0.73% per year (95% CI, 0.27 to 1.19). Statins may reduce the incidence of all strokes without any increase in hemorrhagic strokes, and this effect is mainly driven by the extent of between-group LDL-C reduction. Carotid IMT progression also strongly correlated with LDL-C reduction.