title: Placebo-controlled trial of high-dose atorvastatin in patients with severe cerebral small vessel disease.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Neurology, Stroke Centre, Bichat University Hospital, Denis Diderot University and Medical School, Paris, France.
authors.forename: Philippa C
authors.initials: PC
authors.lastname: Lavallée
authors.forename: Julien
authors.initials: J
authors.lastname: Labreuche
authors.forename: Fernando
authors.initials: F
authors.lastname: Gongora-Rivera
authors.forename: Arturo
authors.initials: A
authors.lastname: Jaramillo
authors.forename: David
authors.initials: D
authors.lastname: Brenner
authors.forename: Isabelle F
authors.initials: IF
authors.lastname: Klein
authors.forename: Pierre-Jean
authors.initials: PJ
authors.lastname: Touboul
authors.forename: Eric
authors.initials: E
authors.lastname: Vicaut
authors.forename: Pierre
authors.initials: P
authors.lastname: Amarenco
mesh_terms: D000368:Aged; D000069059:Atorvastatin; D001794:Blood Pressure / Q000187:drug effects; D001916:Brachial Artery / Q000502:physiology; D002097:C-Reactive Protein / Q000378:metabolism; D002339:Carotid Arteries / Q000187:drug effects / Q000502:physiology; D002560:Cerebrovascular Circulation / Q000502:physiology; D002561:Cerebrovascular Disorders / Q000188:drug therapy* / Q000473:pathology; D016208:Databases, Factual; D004311:Double-Blind Method; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology; D005260:Female; D006538:Heptanoic Acids / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D008055:Lipids / Q000097:blood; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D011758:Pyrroles / Q000008:administration & dosage / Q000627:therapeutic use*; D012307:Risk Factors; D020521:Stroke / Q000188:drug therapy* / Q000473:pathology; D016896:Treatment Outcome; D014664:Vasodilation / Q000502:physiology
chemical_list: D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008055:Lipids; D011758:Pyrroles; D002097:C-Reactive Protein; D000069059:Atorvastatin