Biologic effects of simvastatin in patients with aneurysmal subarachnoid hemorrhage: a double-blind, placebo-controlled randomized trial.
Recently, two randomized controlled phase II studies showed that acute initiation of statin treatment directly after aneurysmal subarachnoid hemorrhage (SAH) decreases the incidence of radiologic vasospasm and clinical signs of delayed cerebral ischemia (DCI), and even reduces mortality. It was hypothesized that the beneficial effect resulted from pleiotropic effects of statins. The purpose of this study was to investigate the biologic effects of acute statin treatment in patients with SAH. We performed an exploratory single-center, prospective, randomized, double-blind, placebo-controlled trial. Patients were randomized to simvastatin 80 mg or placebo once daily. A total of 32 patients were included. There were no statistically significant differences in clinical baseline characteristics. With regard to primary outcomes, there were significant differences by treatment group for total cholesterol and low-density lipoprotein (LDL) cholesterol (P<0.0001), but not for parameters of coagulation, fibrinolysis, endothelium function, and inflammation. With regard to secondary outcomes, no differences were observed in the incidence of transcranial Doppler vasospasm, clinical signs of DCI, and poor outcome. We conclude that both the primary and secondary outcome results of this study do not support a beneficial effect of simvastatin in patients with SAH.
Vergouwen
Mervyn D I
MD
Department of Neurology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, Amsterdam 1105 AZ, The Netherlands. m.d.vergouwen@amc.uva.nl
Meijers
Joost C M
JC
Geskus
Ronald B
RB
Coert
Bert A
BA
Horn
Janneke
J
Stroes
Erik S G
ES
van der Poll
Tom
T
Vermeulen
Marinus
M
Roos
Yvo B W E M
YB
D001777:Blood Coagulation / Q000187:drug effects; D002545:Brain Ischemia / Q000097:blood / Q000209:etiology / Q000517:prevention & control*; D002533:Cerebral Angiography; D002560:Cerebrovascular Circulation / Q000187:drug effects; D008078:Cholesterol, LDL / Q000097:blood; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D000960:Hypolipidemic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D002532:Intracranial Aneurysm / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D018810:Magnetic Resonance Angiography; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D019821:Simvastatin / Q000008:administration & dosage / Q000627:therapeutic use*; D013345:Subarachnoid Hemorrhage / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D013997:Time Factors; D016896:Treatment Outcome
D008078:Cholesterol, LDL; D000960:Hypolipidemic Agents; D019821:Simvastatin