Placebo-controlled trial of high-dose atorvastatin in patients with severe cerebral small vessel disease.
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.
Lavallée
Philippa C
PC
Department of Neurology, Stroke Centre, Bichat University Hospital, Denis Diderot University and Medical School, Paris, France.
Labreuche
Julien
J
Gongora-Rivera
Fernando
F
Jaramillo
Arturo
A
Brenner
David
D
Klein
Isabelle F
IF
Touboul
Pierre-Jean
PJ
Vicaut
Eric
E
Amarenco
Pierre
P
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
D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008055:Lipids; D011758:Pyrroles; D002097:C-Reactive Protein; D000069059:Atorvastatin