To Minh-Son, Prakash Shivesh, Poonnoose Santosh I, Bihari Shailesh
School of Medicine, Flinders University, Bedford Park, SA, Australia.
Department of Critical Care Medicine, Flinders University, Bedford Park, SA, Australia; Department of Intensive and Critical Care Unit, Flinders Medical Centre, Bedford Park, SA, Australia.
World Neurosurg. 2018 May;113:153-162. doi: 10.1016/j.wneu.2018.01.184. Epub 2018 Feb 7.
The study uses meta-regression analysis to quantify the dose-dependent effects of statin pharmacotherapy on vasospasm, delayed ischemic neurologic deficits (DIND), and mortality in aneurysmal subarachnoid hemorrhage.
Prospective, retrospective observational studies, and randomized controlled trials (RCTs) were retrieved by a systematic database search. Summary estimates were expressed as absolute risk (AR) for a given statin dose or control (placebo). Meta-regression using inverse variance weighting and robust variance estimation was performed to assess the effect of statin dose on transformed AR in a random effects model. Dose-dependence of predicted AR with 95% confidence interval (CI) was recovered by using Miller's Freeman-Tukey inverse.
The database search and study selection criteria yielded 18 studies (2594 patients) for analysis. These included 12 RCTs, 4 retrospective observational studies, and 2 prospective observational studies. Twelve studies investigated simvastatin, whereas the remaining studies investigated atorvastatin, pravastatin, or pitavastatin, with simvastatin-equivalent doses ranging from 20 to 80 mg. Meta-regression revealed dose-dependent reductions in Freeman-Tukey-transformed AR of vasospasm (slope coefficient -0.00404, 95% CI -0.00720 to -0.00087; P = 0.0321), DIND (slope coefficient -0.00316, 95% CI -0.00586 to -0.00047; P = 0.0392), and mortality (slope coefficient -0.00345, 95% CI -0.00623 to -0.00067; P = 0.0352).
The present meta-regression provides weak evidence for dose-dependent reductions in vasospasm, DIND and mortality associated with acute statin use after aneurysmal subarachnoid hemorrhage. However, the analysis was limited by substantial heterogeneity among individual studies. Greater dosing strategies are a potential consideration for future RCTs.
本研究采用meta回归分析来量化他汀类药物治疗对动脉瘤性蛛网膜下腔出血患者血管痉挛、迟发性缺血性神经功能缺损（DIND）和死亡率的剂量依赖性影响。
通过系统的数据库检索获取前瞻性、回顾性观察性研究以及随机对照试验（RCT）。汇总估计值表示为给定他汀类药物剂量或对照（安慰剂）的绝对风险（AR）。在随机效应模型中，采用逆方差加权和稳健方差估计进行meta回归，以评估他汀类药物剂量对转换后的AR的影响。使用米勒弗里曼 - 图基逆变换恢复预测AR的剂量依赖性及95%置信区间（CI）。
数据库检索和研究选择标准产生了18项研究（2594例患者）用于分析。其中包括12项RCT、4项回顾性观察性研究和2项前瞻性观察性研究。12项研究调查了辛伐他汀，其余研究调查了阿托伐他汀、普伐他汀或匹伐他汀，辛伐他汀等效剂量范围为20至80毫克。meta回归显示，血管痉挛的弗里曼 - 图基转换后AR呈剂量依赖性降低（斜率系数 -0.00404，95% CI -0.00720至 -0.00087；P = 0.0321），DIND（斜率系数 -0.00316，95% CI -0.00586至 -0.00047；P = 0.0392）和死亡率（斜率系数 -0.00345，95% CI -0.00623至 -0.00067；P = 0.0352）。
本meta回归为动脉瘤性蛛网膜下腔出血后急性使用他汀类药物相关的血管痉挛、DIND和死亡率的剂量依赖性降低提供了薄弱证据。然而，分析受到各研究间显著异质性的限制。更大的给药策略是未来RCT的一个潜在考虑因素。
