title: Simvastatin reduces vasospasm after aneurysmal subarachnoid hemorrhage: results of a pilot randomized clinical trial.
abstract: OBJECTIVE
  Cerebral vasospasm remains a major source of morbidity after aneurysmal subarachnoid hemorrhage (SAH). We demonstrate that simvastatin reduces serum markers of brain injury and attenuates vasospasm after SAH.
  
  
  METHODS
  Patients with angiographically documented aneurysmal SAH were randomized within 48 hours of symptom onset to receive either simvastatin (80 mg daily; n=19) or placebo (n=20) for 14 days. Plasma alanine aminotransferase, aspartate aminotransferase, and creatine phosphokinase were recorded weekly to evaluate laboratory evidence of hepatitis or myositis. Serum markers of brain injury were recorded daily. The primary end point of vasospasm was defined as clinical impression (delayed ischemic deficit not associated with rebleed, infection, or hydrocephalus) in the presence of > or =1 confirmatory radiographic test (angiography or transcranial Doppler demonstrating mean V(MCA) >160 m/sec).
  
  
  RESULTS
  There were no significant differences in laboratory-defined transaminitis or myositis between groups. No patients developed clinical symptoms of myopathy or hepatitis. Plasma von Willebrand factor and S100beta were decreased 3 to 10 days after SAH (P<0.05) in patients receiving simvastatin versus placebo. Highest mean middle cerebral artery transcranial Doppler velocities were significantly lower in the simvastatin-treated group (103+/-41 versus 149+/-47; P<0.01). In addition, vasospasm was significantly reduced (P<0.05) in the simvastatin-treated group (5 of 19) compared with those who received placebo (12 of 20).
  
  
  CONCLUSIONS
  The use of simvastatin as prophylaxis against delayed cerebral ischemia after aneurysmal SAH is a safe and well-tolerated intervention. Its use attenuates serum markers associated with brain injury and decreases the incidence of radiographic vasospasm and delayed ischemic deficit.
authors.affiliation: Departments of Medicine (Neurology), Duke University Medical Center, Durham, NC 27710, USA. lynch004@mc.duke.edu
authors.forename: John R
authors.initials: JR
authors.lastname: Lynch
authors.forename: Haichen
authors.initials: H
authors.lastname: Wang
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: McGirt
authors.forename: James
authors.initials: J
authors.lastname: Floyd
authors.forename: Allan H
authors.initials: AH
authors.lastname: Friedman
authors.forename: Alexander L
authors.initials: AL
authors.lastname: Coon
authors.forename: Robert
authors.initials: R
authors.lastname: Blessing
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Alexander
authors.forename: Carmelo
authors.initials: C
authors.lastname: Graffagnino
authors.forename: David S
authors.initials: DS
authors.lastname: Warner
authors.forename: Daniel T
authors.initials: DT
authors.lastname: Laskowitz
mesh_terms: D000328:Adult; D000368:Aged; D000410:Alanine Transaminase / Q000097:blood; D001219:Aspartate Aminotransferases / Q000097:blood; D001921:Brain / Q000473:pathology; D002545:Brain Ischemia / Q000473:pathology; D003402:Creatine Kinase / Q000097:blood; D004311:Double-Blind Method; D004730:Endothelium, Vascular / Q000378:metabolism; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D007249:Inflammation; D008875:Middle Aged; D015233:Models, Statistical; D010865:Pilot Projects; D019821:Simvastatin / Q000627:therapeutic use*; D013345:Subarachnoid Hemorrhage / Q000188:drug therapy* / Q000473:pathology*; D013997:Time Factors; D016896:Treatment Outcome; D014652:Vascular Diseases / Q000473:pathology; D020301:Vasospasm, Intracranial / Q000188:drug therapy*
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D019821:Simvastatin; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D003402:Creatine Kinase