title: High-dose simvastatin for aneurysmal subarachnoid hemorrhage: multicenter randomized controlled double-blinded clinical trial.
abstract: OBJECTIVE
  Experimental evidence has indicated the benefits of simvastatin for the treatment of subarachnoid hemorrhage. Two randomized placebo-controlled pilot trials that used the highest clinically approved dose of simvastatin (80 mg daily) gave positive results despite the fact that a lower dose of simvastatin (40 mg daily) did not improve clinical outcomes. We hypothesized that a high dose of 80 mg of simvastatin daily for 3 weeks would reduce the incidence of delayed ischemic deficits after subarachnoid hemorrhage compared with a lower dose (40 mg of simvastatin daily) and lead to improved clinical outcomes.
  
  
  METHODS
  The study design was a randomized controlled double-blinded clinical trial. Patients with aneurysmal subarachnoid hemorrhage (presenting within 96 hours of the ictus) from 6 neurosurgical centers were recruited for 3 years. The primary outcome measure was the presence of delayed ischemic deficits, and secondary outcome measures included a modified Rankin disability score at 3 months and an analysis of cost-effectiveness.
  
  
  RESULTS
  No difference was observed between the groups treated with the higher dose or the lower dose of simvastatin in the incidence of delayed ischemic deficits (27% versus 24%; odds ratio, 1.2; 95% confidence interval, 0.7-2.0; P=0.586) or in the rate of favorable outcomes (modified Rankin Scale score, 0-2) at 3 months (73% versus 72%; odds ratio, 1.1; 95% confidence interval, 0.6-1.9; P=0.770).
  
  
  CONCLUSIONS
  High-dose simvastatin treatment should not be prescribed routinely for aneurysmal subarachnoid hemorrhage.
  
  
  BACKGROUND
  http://www.clinicaltrials.gov. Unique identifier: NCT01077206.
authors.affiliation: From the Division of Neurosurgery (G.K.C.W., D.Y.C.C., W.S.P.), Department of Anaesthesia and Intensive Care (M.T.V.C., T.G.), Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China; Department of Diagnostic Imaging, Kwong Wah Hospital, Hong Kong, China (D.Y.W.S.); and Jockey Club School of Public Health and Primary Care, The Chinese University of Hong Kong, Hong Kong, China (B.C.Y.Z., M.L.). georgewong@surgery.cuhk.edu.hk.
authors.forename: George K C
authors.initials: GK
authors.lastname: Wong
authors.affiliation: From the Division of Neurosurgery (G.K.C.W., D.Y.C.C., W.S.P.), Department of Anaesthesia and Intensive Care (M.T.V.C., T.G.), Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China; Department of Diagnostic Imaging, Kwong Wah Hospital, Hong Kong, China (D.Y.W.S.); and Jockey Club School of Public Health and Primary Care, The Chinese University of Hong Kong, Hong Kong, China (B.C.Y.Z., M.L.).
authors.forename: David Y C
authors.initials: DY
authors.lastname: Chan
authors.affiliation: From the Division of Neurosurgery (G.K.C.W., D.Y.C.C., W.S.P.), Department of Anaesthesia and Intensive Care (M.T.V.C., T.G.), Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China; Department of Diagnostic Imaging, Kwong Wah Hospital, Hong Kong, China (D.Y.W.S.); and Jockey Club School of Public Health and Primary Care, The Chinese University of Hong Kong, Hong Kong, China (B.C.Y.Z., M.L.).
authors.forename: Deyond Y W
authors.initials: DY
authors.lastname: Siu
authors.affiliation: From the Division of Neurosurgery (G.K.C.W., D.Y.C.C., W.S.P.), Department of Anaesthesia and Intensive Care (M.T.V.C., T.G.), Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China; Department of Diagnostic Imaging, Kwong Wah Hospital, Hong Kong, China (D.Y.W.S.); and Jockey Club School of Public Health and Primary Care, The Chinese University of Hong Kong, Hong Kong, China (B.C.Y.Z., M.L.).
authors.forename: Benny C Y
authors.initials: BC
authors.lastname: Zee
authors.affiliation: From the Division of Neurosurgery (G.K.C.W., D.Y.C.C., W.S.P.), Department of Anaesthesia and Intensive Care (M.T.V.C., T.G.), Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China; Department of Diagnostic Imaging, Kwong Wah Hospital, Hong Kong, China (D.Y.W.S.); and Jockey Club School of Public Health and Primary Care, The Chinese University of Hong Kong, Hong Kong, China (B.C.Y.Z., M.L.).
authors.forename: Wai S
authors.initials: WS
authors.lastname: Poon
authors.affiliation: From the Division of Neurosurgery (G.K.C.W., D.Y.C.C., W.S.P.), Department of Anaesthesia and Intensive Care (M.T.V.C., T.G.), Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China; Department of Diagnostic Imaging, Kwong Wah Hospital, Hong Kong, China (D.Y.W.S.); and Jockey Club School of Public Health and Primary Care, The Chinese University of Hong Kong, Hong Kong, China (B.C.Y.Z., M.L.).
authors.forename: Matthew T V
authors.initials: MT
authors.lastname: Chan
authors.affiliation: From the Division of Neurosurgery (G.K.C.W., D.Y.C.C., W.S.P.), Department of Anaesthesia and Intensive Care (M.T.V.C., T.G.), Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China; Department of Diagnostic Imaging, Kwong Wah Hospital, Hong Kong, China (D.Y.W.S.); and Jockey Club School of Public Health and Primary Care, The Chinese University of Hong Kong, Hong Kong, China (B.C.Y.Z., M.L.).
authors.forename: Tony
authors.initials: T
authors.lastname: Gin
authors.affiliation: From the Division of Neurosurgery (G.K.C.W., D.Y.C.C., W.S.P.), Department of Anaesthesia and Intensive Care (M.T.V.C., T.G.), Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China; Department of Diagnostic Imaging, Kwong Wah Hospital, Hong Kong, China (D.Y.W.S.); and Jockey Club School of Public Health and Primary Care, The Chinese University of Hong Kong, Hong Kong, China (B.C.Y.Z., M.L.).
authors.forename: Michael
authors.initials: M
authors.lastname: Leung
mesh_terms: D000328:Adult; D000368:Aged; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D019821:Simvastatin / Q000008:administration & dosage*; D013345:Subarachnoid Hemorrhage / Q000175:diagnosis* / Q000188:drug therapy*; D016896:Treatment Outcome
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D019821:Simvastatin
keywords: simvastatin; stroke; subarachnoid hemorrhage