Placebo-controlled trial of high-dose atorvastatin in patients with severe cerebral small vessel disease

Abstract

Background and purpose: Uncontrolled studies have shown that statins can improve cerebral vasoreactivity (CVR) in patients with mild small vessel disease. We sought to determine whether high-dose atorvastatin increases CVR compared with placebo in patients with severe small vessel disease.

Methods: Ninety-four adults with recent lacunar stroke were randomly allocated in a double-blind manner to 80 mg of atorvastatin daily or matching placebo after stratification for hypertensive and diabetic status. The primary end point was change in CVR after 3 months of treatment. Secondary outcomes were changes in brachial and carotid artery endothelial-dependent vasodilations.

Results: At baseline, all patients had a severely impaired CVR (mean, 12.1%; 95% CI, 9.5-14.7) and carotid (mean, -0.25%; 95% CI, -1.17-0.67) and brachial artery (mean, 2.72%; 95% CI, 1.39-4.05) endothelial function. Despite reductions of 55% in low-density lipoprotein cholesterol and of 30% in high-sensitivity C-reactive protein in the active arm compared to placebo, atorvastatin 80 mg per day did not improve CVR or endothelial dysfunction of carotid and brachial arteries.

Conclusions: We found no positive effect of 3-month treatment with atorvastatin on severe cerebral microvasculature endothelial dysfunction in patients with lacunar stroke.

Trial registration: ClinicalTrials.gov NCT00163150.