on March 12, 2009
Published online before print March 12, 2009, doi: 10.1161/STROKEAHA.108.540088
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Submitted on October 16, 2008
From INSERM U-698 and Department of Neurology and Stroke Centre (P.C.L., J.L., F.G.-R., A.J., D.B., P.J.T. P.A.), Bichat University Hospital, Denis Diderot University and Medical School, Paris, France; Neuroradiology Unit (I.F.K.), Department of Radiology, Bichat University Hospital, Denis Diderot University and Medical School, Paris, France; Department of Biostatistics and Clinical Research (E.V.), Fernand Widal University Hospital, Denis Diderot University and Medical School, Paris, France. * To whom correspondence should be addressed. E-mail: pierre.amarenco{at}bch.aphp.fr.
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. Conclusion—We found no positive effect of 3-month treatment with atorvastatin on severe cerebral microvasculature endothelial dysfunction in patients with lacunar stroke.
Accepted on November 27, 2008
Placebo-Controlled Trial of High-Dose Atorvastatin in Patients With Severe Cerebral Small Vessel Disease
Philippa C. Lavallée MD;
Key words: atorvastatin • cerebral vasoreactivity • endothelial dysfunction • lacunar stroke
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