J Korean Neurosurg Soc.  2015 Oct;58(4):328-333. 10.3340/jkns.2015.58.4.328.

High-Dose Simvastatin Is Effective in Preventing Cerebral Vasospasm after Aneurysmal Subarachnoid Hemorrhage: A Prospective Cohort Study in Korean Patients

• Woo SW
• Kim JH
• Kang HI
• Kim DR
• Moon BG
• Kim JS

• KMID: 2114368
• DOI: http://doi.org/10.3340/jkns.2015.58.4.328

Abstract

OBJECTIVE
The goal of this study was to assess the effect of high-dose simvastatin on cerebral vasospasm and its clinical outcome after aneurysmal subarachnoid hemorrhage (SAH) in Korean patients.
METHODS
This study was designed as a prospective observational cohort study. Its subjects were aneurysmal SAH patients who had undergone aneurysm clipping or coiling. They were assigned to 1 of 3 groups : the 20 mg, 40 mg, and 80 mg simvastatin groups. The primary end-point was the occurrence of symptomatic vasospasm. The clinical outcome was assessed with the modified Rankin Scale (mRS) score after 1 month and 3 months. The risk factors of the development of vasospasm were assessed by logistic regression analysis.
RESULTS
Ninety nine patients with aneurysmal SAH were treated and screened. They were sequentially assigned to the 20 mg (n=22), 40 mg (n=34), and 80 mg (n=31) simvastatin groups. Symptomatic vasospasm occurred in 36.4% of the 20 mg group, 8.8% of the 40 mg group, and 3.2% of the 80 mg group (p=0.003). The multiple logistic regression analysis showed that poor Hunt-Hess grades (OR=5.4 and 95% CI=1.09-26.62) and high-dose (80 mg) simvastatin (OR=0.09 and 95% CI=0.1-0.85) were independent factors of symptomatic vasospasm. The clinical outcomes did not show a significant difference among the three groups.
CONCLUSION
This study demonstrated that 80 mg simvastatin treatment was effective in preventing cerebral vasospasm after aneurysmal SAH, but did not improve the clinical outcome in Korean patients.

Keyword

Outcome; Statin; Subarachnoid hemorrhage; Vasospasm

MeSH Terms

Aneurysm*
Cohort Studies*
Humans
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Logistic Models
Prospective Studies*
Risk Factors
Simvastatin*
Subarachnoid Hemorrhage*
Vasospasm, Intracranial*
Simvastatin

Figure

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  Fig. 1 Diagram showing study design. The reasons for exclusion are as follows : 1) Ten patients died within 14 days after ictus. 2) Two patients were transferred to pulmonary medicine due to lung diseases, thus had insufficient data about the occurrence of vasospasm. 3) Two patients had statin side effects. One patient (40 mg group) showed elevated liver transaminase up to 200 U/L. Another patient (80 mg group) complained muscle cramp of legs and creatine phosphokinase elevated to 1200 U/L. After cessation of statin, laboratory values were normalized within 3 days.

• 

  Fig. 2 Bar graph showing the incidence of symptomatic vasospasm between 20 mg and 80 mg simvastatin group (A) and between 40 mg and 80 mg simvastatin group (B).

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