Simvastatin for the prevention of symptomatic cerebral vasospasm following aneurysmal subarachnoid hemorrhage: a single-institution prospective cohort study

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  • Department of Neurosurgery, Johns Hopkins University Hospital, Baltimore, Maryland
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Object

Vasospasm is the major cause of disability and death after aneurysmal subarachnoid hemorrhage (aSAH). Although the results of 2 randomized clinical trials demonstrated that statin decreases the incidence of symptomatic cerebral vasospasm after aSAH, retrospective studies have failed to confirm this. The authors conducted a prospective observational study to determine whether a standardized regimen of simvastatin would reduce the incidence of cerebral vasospasm and improve neurological outcomes in patients with aSAH.

Methods

Since 1991, all patients with aSAH admitted to the authors' institution have been prospectively followed up with standardized outcomes recording. Starting in September 2005, all patients admitted with aSAH were given enteral simvastatin (80 mg/day for 14 days) in addition to the standard care. The incidence of symptomatic cerebral vasospasm, length of hospitalization, in-hospital mortality rate, and discharge Glasgow Outcome Scale scores in these 170 patients were compared to data obtained in 170 consecutive patients who underwent treatment in our unit prior to the introduction of statin therapy.

Results

The 5-year study period included 340 consecutively treated patients (170 who received statins and 170 who did not). Patients who received simvastatin therapy were more frequently male (29 vs 20%) and had a smaller median aneurysm diameter (6 vs 7 mm). Baseline characteristics were otherwise similar between the cohorts. There were no differences in the incidence of symptomatic vasospasm (25.3 vs 30.5%; p = 0.277), in-hospital mortality rate (18 vs 15%; p = 0.468), length of hospitalization (21 ± 15 vs 19 ± 12 days; p = 0.281), or poor outcome at discharge (Glasgow Outcome Scale Scores 1–2: 21.7 vs 18.2%; p = 0.416) between the simvastatin and nonstatin cohorts. There were no statin-related complications.

Conclusions

The uniform introduction of simvastatin did not reduce the incidence of symptomatic cerebral vasospasm, death, or poor outcome in patients with aSAH. Simvastatin was well tolerated, but its benefit may be less than has been previously reported.

Abbreviations used in this paper: aSAH = aneurysmal subarachnoid hemorrhage; eNOS = endothelial nitric oxide synthase; GOS = Glasgow Outcome Scale; H & H = Hunt and Hess; HHH = hypertensive, hypervolemic, hemodilutional; IQR = interquartile range; SAH = subarachnoid hemorrhage; TCD = Transcranial Doppler.

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Contributor Notes

Address correspondence to: Rafael J. Tamargo, M.D., The Johns Hopkins University Hospital, Department of Neurosurgery, 600 North Wolfe Street, Meyer 8-181, Baltimore, Maryland 21287. email: rtamarg1@jhmi.edu.
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