Statin treatment of cerebral vasospasm after aneurysmal subarachnoid hemorrhage

OBJECTIVE: To evaluate the evidence for use of hydroxymethylglutaryl coenzyme A reductase inhibitors (statins) for the prevention and management of cerebral vasospasm after aneurysmal subarachnoid hemorrhage (aSAH). DATA SOURCES: Literature searches were conducted using MEDLINE (1966-July 2007) and the Cochrane Database (2007, Issue 2). Search terms included HMG-CoA reductase inhibitors, statins, subarachnoid hemorrhage, and vasospasm. Other data sources were identified from select bibliographies. STUDY SELECTION AND DATA EXTRACTION: All controlled trials evaluating statins for the prevention and management of cerebral vasospasm after aSAH and published in the English language were included for review. Clinical and surrogate markers for cerebral vasospasm and outcomes were assessed. DATA SYNTHESIS: Cerebral vasospasm, which may occur after aSAH, is associated with serious morbidity and significant mortality. Evidence suggests that statins have noteworthy biochemical effects through inhibition of nicotinamide adenine dinucleotide phosphate oxidase and superoxide production and up-regulation and activation of endothelial nitric oxidase synthase and nitric oxidase production via inhibition of geranylgeranylation of RhoA and Rac1 guanosine triphosphatases. Researchers have proposed that these effects may have a role in preventing or reducing vasospasm after aSAH. One matched control study and 3 placebo-controlled trials (1 with an additional post hoc analysis) have described use of statins for the prevention and management of cerebral vasospasm after aSAH. These data focused on differing primary endpoints; however, reductions in clinical vasospasm and middle cerebral artery transcranial doppler velocity, improved functional outcomes, enhanced autoregulation indices incidence, improvements in duration and time of impaired cerebral autoregulation, and reductions in rescue therapy have been reported. CONCLUSIONS: Current data suggest that statins may be a reasonable treatment option for the prevention and management of cerebral vasospasm after aSAH. However, results from large, well-controlled trials have not been published.