Early High-dosage Atorvastatin Treatment Improved Serum Immune-inflammatory Markers and Functional Outcome in Acute Ischemic Strokes Classified as Large Artery Atherosclerotic Stroke: A Randomized Trial

Medicine (Baltimore). 2016 Mar;95(13):e3186. doi: 10.1097/MD.0000000000003186.

Abstract

Statins have beneficial effects on cerebral circulation and brain parenchyma during ischemic stroke and reperfusion. The primary hypothesis of this randomized parallel trial was that treatment with 80 mg/day of atorvastatin administered early at admission after acute atherosclerotic ischemic stroke could reduce serum levels of markers of immune-inflammatory activation of the acute phase and that this immune-inflammatory modulation could have a possible effect on prognosis of ischemic stroke evaluated by some outcome indicators. We enrolled 42 patients with acute ischemic stroke classified as large arteries atherosclerosis stroke (LAAS) randomly assigned in a randomized parallel trial to the following groups: Group A, 22 patients treated with atorvastatin 80 mg (once-daily) from admission day until discharge; Group B, 20 patients not treated with atorvastatin 80 mg until discharge, and after discharge, treatment with atorvastatin has been started. At 72 hours and at 7 days after acute ischemic stroke, subjects of group A showed significantly lower plasma levels of tumor necrosis factor-α, interleukin (IL)-6, vascular cell adhesion molecule-1, whereas no significant difference with regard to plasma levels of IL-10, E-Selectin, and P-Selectin was observed between the 2 groups. At 72 hours and 7 days after admission, stroke patients treated with atorvastatin 80 mg in comparison with stroke subjects not treated with atorvastatin showed a significantly lower mean National Institutes of Health Stroke Scale and modified Rankin scores. Our findings provide the first evidence that atorvastatin acutely administered immediately after an atherosclerotic ischemic stroke exerts a lowering effect on immune-inflammatory activation of the acute phase of stroke and that its early use is associated to a better functional and prognostic profile.

Trial registration: ClinicalTrials.gov NCT02225834.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Acute Disease
  • Aged
  • Atorvastatin / pharmacology
  • Atorvastatin / therapeutic use*
  • Biomarkers
  • Brain Ischemia / drug therapy*
  • Brain Ischemia / etiology
  • Brain Ischemia / physiopathology
  • E-Selectin / biosynthesis
  • Female
  • Humans
  • Inflammation / drug therapy*
  • Inflammation / physiopathology
  • Inflammation Mediators / metabolism*
  • Intercellular Adhesion Molecule-1 / biosynthesis
  • Interleukin-10 / biosynthesis
  • Interleukin-1beta / biosynthesis
  • Interleukin-6 / biosynthesis
  • Intracranial Arteriosclerosis / complications
  • Male
  • Middle Aged
  • P-Selectin / biosynthesis
  • Stroke / drug therapy*
  • Stroke / etiology
  • Stroke / physiopathology
  • Tumor Necrosis Factor-alpha / biosynthesis
  • Vascular Cell Adhesion Molecule-1 / biosynthesis

Substances

  • Biomarkers
  • E-Selectin
  • Inflammation Mediators
  • Interleukin-1beta
  • Interleukin-6
  • P-Selectin
  • Tumor Necrosis Factor-alpha
  • Vascular Cell Adhesion Molecule-1
  • Intercellular Adhesion Molecule-1
  • Interleukin-10
  • Atorvastatin

Associated data

  • ClinicalTrials.gov/NCT02225834