Published Online
on July 28, 2005

A more recent version of this article appeared on September 1, 2005

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Submitted on May 19, 2005
Revised on May 19, 2005
Accepted on June 14, 2005

Simvastatin Reduces Vasospasm After Aneurysmal Subarachnoid Hemorrhage. Results of a Pilot Randomized Clinical Trial

John R. Lynch MD^*; Haichen Wang MD; Matthew J. McGirt MD; James Floyd BS; Allan H. Friedman MD; Alexander L. Coon MD; Robert Blessing CRNP; Michael J. Alexander MD; Carmelo Graffagnino MD; David S. Warner MD; and Daniel T. Laskowitz MD, MHS

From the Departments of Medicine (Neurology) (J.R.L., H.W., R.B., C.G., D.T.L.), Surgery (Neurosurgery) (A.H.F., M.J.A., D.S.W., D.T.L.), and Anesthesiology (D.S.W., D.T.L.), Duke University Medical Center, Durham, NC; Department of Neurosurgery (H.W., M.J.M., A.L.C.), The Johns Hopkins Hospital, Baltimore, MD; Duke University School of Medicine (J.F.), Durham, NC; and Multidisciplinary Neuroprotection Laboratory (J.R.L., D.S.W., D.T.L.), Durham, NC.

^* To whom correspondence should be addressed. E-mail: lynch004{at}mc.duke.edu.

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 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 S100 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).

Conclusion--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.

Key words: HMG-CoA reductase inhibitors • inflammation • subarachnoid hemorrhage • vasospasm, intracranial

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