脑血疏口服液治疗高血压性脑出血有效性及安全性的系统评价与Meta分析

Systematic review and Meta-analysis on efficacy and safety of Naoxueshu Oral Liquid in treatment of hypertensive intracerebral hemorrhage

为系统评价脑血疏口服液治疗高血压性脑出血的疗效和安全性,检索四大中文数据库、四大英文数据库、ClinicalTrials.gov及中国临床试验注册系统,检索建库至2020年9月9日。按照预定标准筛选脑血疏口服液联合常规西药治疗高血压性脑出血的随机对照试验(RCT)。采用Cochrane偏倚风险评估工具对纳入文献进行评价,应用RevMan 5.4.1软件进行Meta分析,并采用GRADE系统对结局指标进行证据质量评价。最终纳入11项研究,总样本量1221例,试验组612例,对照组609例。结果显示,脑血疏口服液联合常规西药在高血压性脑出血治疗2周后降低美国国立卫生研究所卒中量表(NIHSS)评分与常规西药相比无明显差异(MD=-1.59,95%CI[-3.46,0.29],P=0.10),治疗30 d后优于常规西药(MD=-1.16,95%CI[-1.39,-0.94],P<0.00001);提高格拉斯哥昏迷量表(GCS)评分优于常规西药(MD=1.00,95%CI[0,2.00],P=0.05);提高Barthel指数(Barthel index,BI)与常规西药相比无明显差异(MD=1.00,95%CI[-0.30,2.30],P=0.13);降低二次脑损伤(SBI)发生率优于常规西药(RR=0.38,95%CI[0.24,0.59],P<0.0001)。有效率方面,采用《中药新药临床研究指导原则》、NHISS或格拉斯哥预后分级(GOS)为标准的研究均表明优于常规西药(RR《中药新药临床研究指导原则》=1.27,95%CI[1.10,1.46],P=0.001;RRNHISS=1.26,95%CI[1.13,1.40],P<0.0001;RRGOS=1.54,95%CI[1.22,1.93],P=0.0002),治疗2周及4周时血肿体积吸收优于常规西药(MD2周=-2.31,95%CI[-3.12,-1.49],P<0.00001;MD4周=-2.04,95%CI[-2.41,-1.68],P<0.00001)。GRADE评价显示上述结局指标的证据质量分别为低和极低。不良反应方面,纳入文献中有2项报告的不良反应均为轻度不良反应,其余文献未提及,故该研究尚不能对脑血疏口服液的安全性做出肯定性评价。结果表明,与常规西药相比,联合使用脑血疏口服液治疗高血压性脑出血可能更佳,但鉴于纳入文献偏倚风险较高,今后仍需更多大样本、高质量的随机对照试验予以完善。

To systematically review the efficacy and safety of Naoxueshu Oral Liquid in treatment of hypertensive intracerebral hemorrhage,four Chinese databases,four English databases,clinical trials registration center(ClinicalTrials.gov)and Chinese clinical trial registry were retrieved.The retrieval time was from the establishment of each database to September 9,2020.According to the set criteria,the randomized controlled trial(RCT)of Naoxueshu Oral Liquid combined with conventional Western medicine was selected.The"Cochrane bias risk assessment"tool was used to evaluate the quality of the included studies.RevMan 5.4.1 was used to conduct Meta-analysis of the included studies and GRADE system was used to evaluate the evidence quality of the outcome indicators.Eleven studies were finally included,with a total sample size of 1221 cases,612 cases in the treatment group and 609 cases in the control group.Meta-analysis showed that Naoxueshu Oral Liquid combined with conventional Western medicine had no significant difference compare with conventional Western medicine in reducing National Institute of health stroke scale(NIHSS)after 2 weeks of treatment for hypertensive intracerebral hemorrhage(MD=-1.59,95%CI[-3.46,0.29],P=0.10),but was superior to conventional Western medicine after 30 d of treatment(MD=-1.16,95%CI[-1.39,-0.94],P<0.00001).Naoxueshu Oral Liquid combined with conventional Western medicine was superior to conventional Western medicine in improving Glasgow coma scale(MD=1.00,95%CI[0,2.00],P=0.05)and reducing the incidence of secondary brain insults(RR=0.38,95%CI[0.24,0.59],P<0.0001),but there was no significant difference in increasing Barthel index(MD=1.00,95%CI[-0.30,2.30],P=0.13).In terms of effective rate,studies using Guideline for clinical trials of new patent Chinese medicines,NHISS or Glasgow outcome scale(GOS)had shown that Naoxueshu Oral Liquid combined with conventional Western medicine was superior to conventional Western medicine(RRGuideline for clinical trials of new patent Chinese medicines=1.27,95%CI[1.10,1.46],P=0.001;RRNHISS=1.26,95%CI[1.13,1.40],P<0.0001;RRGOS=1.54,95%CI[1.22,1.93],P=0.0002).In reduction of hematoma volume,Naoxueshu Oral Liquid combined with conventional Western medicine was superior to conventional Western medicine after 2 and 4 weeks of treatment(MD2 week=-2.31,95%CI[-3.12,-1.49],P<0.00001;MD4 week=-2.04,95%CI[-2.41,-1.68],P<0.00001).GRADE system showed that the evidence level of the above outcome indicators was low and extremely low.In terms of adverse reactions,two of the included studies reported mild adverse reactions,and the rest of studies were not mentioned,so this study was not able to make a positive evaluation of the safety of Naoxueshu Oral Liquid.This study showed that compared with conventional Western medicine,combined Naoxueshu Oral Liquid may be better for hypertensive intracerebral hemorrhage.However,due to the high bias risk in the included studies,more large-sample and high-quality RCTs are still needed in the future.