From the Department of Neurological Surgery (C.-J.C., N.I., T.J.B.), University of Virginia Health System, Charlottesville, VA; Department of Neurological Surgery (D.D., R.F.J.), University of Louisville School of Medicine, Louisville, KY; Clinical Trials Office (L.J.E., A.W.), University of Virginia School of Medicine; Department of Pharmacology (A.P.A.), University of Virginia Health System, Charlottesville, VA; Department of Public Health Sciences (S.J.R., B.B.W., A.M.S.), University of Virginia School of Medicine, Charlottesville, VA; Department of Neurosurgery (N.S.N.), Baptist Health, Jacksonville, FL; and Department of Neurology (B.B.W., K.C.J., A.M.S.), University of Virginia Health System, Charlottesville, VA.
Neurology. 2019 Dec 10;93(24):1056-1066. doi: 10.1212/WNL.0000000000008627. Epub 2019 Nov 11.
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.
他汀类药物是治疗血脂异常的常用药物类别，通过靶向周围脑实质中的继发性脑损伤途径，可能对自发性脑出血 (ICH) 具有神经保护作用。他汀类药物的神经保护作用可能源于甲羟戊酸及其衍生物的下调，靶向控制增殖、黏附、迁移、细胞因子产生和活性氧生成的关键细胞信号通路。临床前研究一致表明他汀类药物具有神经保护和恢复增强作用，包括改善神经功能、减少脑水肿、增加血管生成和神经发生、加速血肿清除以及减少炎症细胞浸润。回顾性临床研究报告称，ICH 前服用他汀类药物的患者血肿周围水肿减轻、死亡率降低、功能结局改善。几项临床研究还观察到，ICH 后继续或开始使用他汀类药物的患者死亡率降低、功能结局改善。先前随机试验的亚组分析引起了人们对先前患有出血性中风的患者使用他汀类药物可能会增加复发性 ICH 风险的担忧。然而，大多数他汀类药物试验未能表明他汀类药物使用与出血性中风风险增加之间存在关联。他汀类药物剂量的变化、ICH 前使用他汀类药物以及选择偏倚限制了对他汀类药物对 ICH 后结局影响的严格调查。需要未来的前瞻性试验来研究他汀类药物使用与 ICH 结局之间的关系。
