High-Dose Simvastatin for Aneurysmal Subarachnoid Hemorrhage
Multicenter Randomized Controlled Double-Blinded Clinical Trial
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.
- Received August 7, 2014.
- Revision received October 15, 2014.
- Accepted November 13, 2014.
- © 2014 American Heart Association, Inc.