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

Stroke. 2009 May;40(5):1721-8. doi: 10.1161/STROKEAHA.108.540088. Epub 2009 Mar 12.

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.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Atorvastatin
  • Blood Pressure / drug effects
  • Brachial Artery / physiology
  • C-Reactive Protein / metabolism
  • Carotid Arteries / drug effects
  • Carotid Arteries / physiology
  • Cerebrovascular Circulation / physiology
  • Cerebrovascular Disorders / drug therapy*
  • Cerebrovascular Disorders / pathology
  • Databases, Factual
  • Double-Blind Method
  • Endothelium, Vascular / drug effects
  • Endothelium, Vascular / physiology
  • Female
  • Heptanoic Acids / administration & dosage
  • Heptanoic Acids / therapeutic use*
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / administration & dosage
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use*
  • Lipids / blood
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Pyrroles / administration & dosage
  • Pyrroles / therapeutic use*
  • Risk Factors
  • Stroke / drug therapy*
  • Stroke / pathology
  • Treatment Outcome
  • Vasodilation / physiology

Substances

  • Heptanoic Acids
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Lipids
  • Pyrroles
  • C-Reactive Protein
  • Atorvastatin

Associated data

  • ClinicalTrials.gov/NCT00163150