QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Résumé Extracto Full Text PDF For Our Patients Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Articles Ahead of Print [Order Reprint] Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Trimble, J. L Articles by Kockler, D. R Search for Related Content PubMed PubMed Citation Articles by Trimble, J. L Articles by Kockler, D. R

DRUG INFORMATION ROUNDS

Statin Treatment of Cerebral Vasospasm after Aneurysmal Subarachnoid Hemorrhage

Clinical Pharmacist, Department of Pharmacy, Sharp Memorial Hospital, San Diego, CA

Denise R Kockler, PharmD BCPS

Director, Drug Information Services, Virginia Commonwealth University Health System/Medical College of Virginia Hospitals; Assistant Clinical Professor, School of Pharmacy, Virginia Commonwealth University, Richmond, VA

Reprints: Dr. Kockler, Medical College of Virginia/VCU, 401 N. 12th St., PO 980042, Richmond, VA 23298, fax 804/225-3919, 9dkockle{at}vcu.edu.

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.

Key Words: HMG-CoA reductase inhibitors, statins, subarachnoid hemorrhage, vasospasm

Published Online, November 6, 2007. www.theannals.com, DOI 10.1345/aph.1K301