Faculty Collaboration Database

Simvastatin reduces vasospasm after aneurysmal subarachnoid hemorrhage: results of a pilot randomized clinical trial. Stroke 2005 Sep;36(9):2024-6

Date

07/30/2005

Pubmed ID

16051891

DOI

10.1161/01.STR.0000177879.11607.10

Scopus ID

2-s2.0-24644488726 (requires institutional sign-in at Scopus site)   247 Citations

Abstract

BACKGROUND AND PURPOSE: 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.

Author List

Lynch JR, Wang H, McGirt MJ, Floyd J, Friedman AH, Coon AL, Blessing R, Alexander MJ, Graffagnino C, Warner DS, Laskowitz DT

MESH terms used to index this publication - Major topics in bold

Adult
Aged
Alanine Transaminase
Aspartate Aminotransferases
Brain
Brain Ischemia
Creatine Kinase
Double-Blind Method
Endothelium, Vascular
Humans
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Inflammation
Middle Aged
Models, Statistical
Pilot Projects
Simvastatin
Subarachnoid Hemorrhage
Time Factors
Treatment Outcome
Vascular Diseases
Vasospasm, Intracranial