High-Dose Simvastatin for Aneurysmal Subarachnoid Hemorrhage: Multicenter Randomized Controlled Double-Blinded Clinical Trial

• Published in: Stroke (1970) Vol. 46; no. 2; pp. 382 - 388
• Main Authors: Wong, George K.C, Chan, David Y.C, Siu, Deyond Y.W, Zee, Benny C.Y, Poon, Wai S, Chan, Matthew T.V, Gin, Tony, Leung, Michael, Zhu, X.L, Liang, M, Tan, H.B, Lee, M.W, Wong, C.K, Chan, T.K, Po, Y.C, Woo, P.Y, Chan, K.Y
• Format: Journal Article
• Language: English
• Published: United States American Heart Association, Inc 01-02-2015
• Subjects: Adult; Aged; Double-Blind Method; Female; Follow-Up Studies; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors - administration & dosage; Male; Middle Aged; Simvastatin - administration & dosage; Subarachnoid Hemorrhage - diagnosis; Subarachnoid Hemorrhage - drug therapy; Treatment Outcome; simvastatin; stroke; subarachnoid hemorrhage
• ISSN: 0039-2499; 1524-4628
• DOI: 10.1161/STROKEAHA.114.007006

BACKGROUND AND PURPOSE—Experimental evidence has indicated the benefits of simvastatin for the treatment of subarachnoid hemorrhage. Two randomized placebo-controlled pilot trials that used the highest clinically approved dose of simvastatin (80 mg daily) gave positive results despite the fact that a lower dose of simvastatin (40 mg daily) did not improve clinical outcomes. We hypothesized that a high dose of 80 mg of simvastatin daily for 3 weeks would reduce the incidence of delayed ischemic deficits after subarachnoid hemorrhage compared with a lower dose (40 mg of simvastatin daily) and lead to improved clinical outcomes.
METHODS—The study design was a randomized controlled double-blinded clinical trial. Patients with aneurysmal subarachnoid hemorrhage (presenting within 96 hours of the ictus) from 6 neurosurgical centers were recruited for 3 years. The primary outcome measure was the presence of delayed ischemic deficits, and secondary outcome measures included a modified Rankin disability score at 3 months and an analysis of cost-effectiveness.
RESULTS—No difference was observed between the groups treated with the higher dose or the lower dose of simvastatin in the incidence of delayed ischemic deficits (27% versus 24%; odds ratio, 1.2; 95% confidence interval, 0.7–2.0; P=0.586) or in the rate of favorable outcomes (modified Rankin Scale score, 0–2) at 3 months (73% versus 72%; odds ratio, 1.1; 95% confidence interval, 0.6–1.9; P=0.770).
CONCLUSIONS—High-dose simvastatin treatment should not be prescribed routinely for aneurysmal subarachnoid hemorrhage.
CLINICAL TRIAL REGISTRATION—URLhttp://www.clinicaltrials.gov. Unique identifierNCT01077206.