Effects of statins on progression of subclinical brain infarct.

BACKGROUND: Subclinical brain infarct (SBI) is associated with subsequent stroke and cognitive decline. A longitudinal epidemiological study suggests that statins may prevent development of SBI. We investigated the effects of statins upon development of brain infarct by performing a post-hoc analysis of the Regression of Cerebral Artery Stenosis (ROCAS) study. METHODS: The ROCAS study is a randomized, double-blind, placebo-controlled study evaluating the effects of simvastatin 20 mg daily upon progression of asymptomatic middle cerebral artery stenosis among stroke-free individuals over 2 years. A total of 227 subjects were randomized to either placebo (n = 114) or simvastatin 20 mg daily (n = 113). The number of brain infarcts as detected by MRI was recorded at baseline and at the end of the study. The primary outcome measure was the number of new brain infarcts at the end of the study. RESULTS: Among the 227 randomized subjects, 33 (14.5%) had SBI at baseline. At the end of the study, significantly fewer subjects in the active group (n = 1) had new brain infarcts compared with the placebo group (n = 8; p = 0.018). The new brain infarcts of subjects in the active group were subclinical. Among the placebo group, the new brain infarcts of 3 subjects were symptomatic while those of the remaining 5 subjects were subclinical. Among putative variables, multivariate regression analysis showed that only the baseline number of SBIs (OR = 6.27, 95% CI 2.4-16.5) and simvastatin treatment (OR = 0.09, 95% CI 0.01-0.82) independently predicted the development of new brain infarcts. CONCLUSIONS: Consistent with findings of the epidemiological study, our study suggests that statins may prevent the development of a new brain infarct.

Statins for asymptomatic middle cerebral artery stenosis: The Regression of Cerebral Artery Stenosis study.

BACKGROUND: The progression of cerebral atherosclerosis increases the risk of stroke and vascular events. Given the known benefits of statins in retarding coronary and carotid atherosclerosis progression, we studied the effects of statins on asymptomatic middle cerebral artery (MCA) stenosis progression. METHODS: We conducted a randomized, double-blind, placebo-controlled study to evaluate the effects of simvastatin on the progression of MCA stenosis among stroke-free individuals who had mild to moderately elevated LDL cholesterol (3.0-5.0 mmol/l). Two hundred and twenty-seven subjects were randomized to either placebo (n = 114) or simvastatin 20 mg daily (n = 113). The severity of MCA stenosis at baseline and at the end of the study was graded by MRA into normal, minimal (<10%), mild (10-49%), moderate (50-90%) and severe (>90%). The primary outcome was the change in grading of MCA stenosis over 2 years. RESULTS: At the end of the study, the LDL cholesterol level decreased by 1.43 and 0.12 mmol/l for the active and placebo groups, respectively (p < 0.001). There was no significant difference in the proportion of patients having stable, progressive and regressive MCA stenosis between the placebo (72, 22 and 6%) and active groups (78.6, 15.5 and 5.8%). The all-cause mortality was significantly lower in the active group (n = 0) relative to the placebo group (n = 7, p = 0.014). Any clinical events were also lower in the active group (n = 5) than in the placebo group (n = 13, p = 0.052). CONCLUSIONS: Simvastatin 20 mg daily had no apparent effect upon the evolution of asymptomatic MCA stenosis over 2 years.

Effects of statins on the progression of cerebral white matter lesion: Post hoc analysis of the ROCAS (Regression of Cerebral Artery Stenosis) study.

Arteriosclerotic related cerebral white matter lesion (WML) is associated with increased risk of death, stroke, dementia, depression, gait disturbance, and urinary incontinence. We investigated the effects of statins on WML progression by performing a post hoc analysis on the ROCAS (Regression of Cerebral Artery Stenosis) study, which is a randomized, double-blind, placebo-controlled study evaluating the effects of statins upon asymptomatic middle cerebral artery stenosis progression among stroke-free individuals. Two hundreds and eight randomized subjects were assigned to either placebo (n = 102) or simvastatin 20 mg daily (n = 106) for 2 years. Baseline severity of WML was graded visually into none, mild, and severe. Volume (cm3) of WML was determined quantitatively at baseline and at end of study using a semi-automated method based on MRI. Primary outcome was the change in WML volume over 2 years. After 2 years of follow-up, there was no significant change in WML volume between the active and the placebo group as a whole. However, stratified analysis showed that for those with severe WML at baseline, the median volume increase in the active group (1.9 cm3) was less compared with that in the placebo group (3.0 cm3; P = 0.047). Linear multivariate regression analysis identified that baseline WML volume (beta = 0.63, P < 0.001) and simvastatin treatment (beta = -0.214, P = 0.043) independently predicted change in WML volume. Our findings suggest that statins may delay the progression of cerebral WML only among those who already have severe WML at baseline.