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Abstract
Statins, a common drug class for treatment of dyslipidemia, may be neuroprotective for spontaneous intracerebral hemorrhage (ICH) by targeting secondary brain injury pathways in the surrounding brain parenchyma. Statin-mediated neuroprotection may stem from downregulation of mevalonate and its derivatives, targeting key cell signaling pathways that control proliferation, adhesion, migration, cytokine production, and reactive oxygen species generation. Preclinical studies have consistently demonstrated the neuroprotective and recovery enhancement effects of statins, including improved neurologic function, reduced cerebral edema, increased angiogenesis and neurogenesis, accelerated hematoma clearance, and decreased inflammatory cell infiltration. Retrospective clinical studies have reported reduced perihematomal edema, lower mortality rates, and improved functional outcomes in patients who were taking statins before ICH. Several clinical studies have also observed lower mortality rates and improved functional outcomes in patients who were continued or initiated on statins after ICH. Subgroup analysis of a previous randomized trial has raised concerns of a potentially elevated risk of recurrent ICH in patients with previous hemorrhagic stroke who are administered statins. However, most statin trials failed to show an association between statin use and increased hemorrhagic stroke risk. Variable statin dosing, statin use in the pre-ICH setting, and selection biases have limited rigorous investigation of the effects of statins on post-ICH outcomes. Future prospective trials are needed to investigate the association between statin use and outcomes in ICH.
Glossary
- BBB=
- blood-brain barrier;
- DC=
- dendritic cell;
- eNOS=
- endothelial nitric oxide synthase;
- FPP=
- farnesyl pyrophosphate;
- GGPP=
- geranylgeranyl pyrophosphate;
- HMG-CoA=
- 3-hydroxy-3-methylglutaryl coenzyme A;
- ICH=
- intracerebral hemorrhage;
- IL=
- interleukin;
- mRS=
- modified Rankin Scale;
- NIHSS=
- NIH Stroke Scale;
- PHE=
- perihematomal edema;
- RBC=
- red blood cell;
- SPARCL=
- Stroke Prevention by Aggressive Reduction in Cholesterol Level;
- TNF=
- tumor necrosis factor
Footnotes
Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
- Received February 22, 2019.
- Accepted in final form July 24, 2019.
- © 2019 American Academy of Neurology
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