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.