养血清脑颗粒治疗偏头痛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 Yangxue Qingnao Granules in treatment of migraine

系统评价养血清脑颗粒单用或联合钙通道阻滞剂对比单独使用钙通道阻滞剂治疗偏头痛的疗效和安全性。该研究检索四大中文数据库(CNKI,VIP,WanFang,CBM),三大英文数据库(Cochrane Library,EMbase,Medline),临床试验注册中心(ClinicalTrials.gov),检索时间为各数据库建库至2020年1月8日。按照设定的纳入标准和排除标准筛选出单用养血清脑颗粒或联合使用钙通道阻滞剂,治疗偏头痛的随机对照试验(randomized controlled trial,RCT)。并采用"Cochrane偏倚风险评估"工具对所纳入的研究进行质量评价,应用RevMan 5.3对纳入的研究进行Meta定量分析并采用GRADE系统对结局指标进行证据质量评价。共检索出583篇文献,最终纳入23项研究,总样本量2308例,治疗组1171例,对照组1137例。所纳入的研究总体质量不高。Meta分析结果显示,(1)有效率方面,养血清脑颗粒联合钙通道阻滞剂优于钙通道阻滞剂(RR=1.24,95%CI[1.17,1.32],P<0.00001),单用养血清脑颗粒与钙通道阻滞剂对比,差异无统计学意义(RR=1.36,95%CI[0.91,2.03],P=0.14);(2)减少头痛频率方面,当头痛频率单位为次/月时,养血清脑颗粒联合钙通道阻滞剂优于钙通道阻滞剂(MD=-1.39,95%CI[-1.83,-0.95],P<0.00001);当头痛频率单位为次/d时,养血清脑颗粒联合钙通道阻滞剂优于钙通道阻滞剂(MD=-2.08,95%CI[-2.34,-1.82],P<0.00001);(3)减轻头痛强度方面,当头痛强度以疼痛强度评分时,养血清脑颗粒联合钙通道阻滞剂优于钙通道阻滞剂(MD=-0.70,95%CI[-0.81,-0.59],P<0.00001);以视觉模拟评定VAS评分时,养血清脑颗粒联合钙通道阻滞剂优于钙通道阻滞剂(MD=-1.59,95%CI[-2.13,-1.06],P<0.00001);(4)减少头痛持续时间方面,养血清脑颗粒联合钙通道阻滞剂优于钙通道阻滞剂(SMD=-3.13,95%CI[-4.12,-2.15],P<0.00001)。GRADE系统显示以上结局指标证据级别为低和极低。不良反应/事件的发生发面,共报告12例,均为轻度不良反应。结果表明,与单用钙通道阻滞剂相比,联合使用养血清脑颗粒可提高有效率、降低头痛发作频率、减轻头痛强度、减少头痛持续时间,并且安全性好,不良反应/事件发生率低;而单独使用养血清脑颗粒与钙通道阻滞剂相比,有效率无差异。但鉴于该次纳入的研究质量较低,影响结论的可靠性,故需谨慎使用该研究的结论,今后仍需更多高质量、大样本、多中心、双盲随机对照试验进一步验证,为临床用药做出更好的建议。

To evaluate the efficacy and safety of Yangxue Qingnao Granules alone or combined with calcium channel blocker in treatment of migraine.In this study,four Chinese databases(CNKI,VIP,WanFang,CBM),three English databases(Cochrane Library,EMbase,Medline)and clinical trials registration center(ClinicalTrials.gov)were retrieved.The retrieval time was from the establishment of each database to January 8,2020.According to the set inclusion criteria and exclusion criteria,the randomized controlled trial(RCT)of Yangxue Qingnao Granules alone or combined with calcium channel blocker was selected.The"Cochrane bias risk assessment"tool was used to evaluate the quality of the included studies.RevMan 5.3 was used to conduct Meta-analysis of the included studies and grade system was used to evaluate the evidence quality of the outcome indicators.A total of 583 documents were retrieved and finally included in 23 studies,with a total sample size of 2308 cases,1171 cases in the treatment group and 1137 cases in the control group.The overall quality of the research included was not high.Meta-analysis showed that,(1)in terms of effective rate,Yangxue Qingnao Granules combined with calcium channel blocker was better than calcium channel blocker(RR=1.24,95%CI[1.17,1.32],P<0.00001),and there was no significant difference between Yangxue Qingnao Granules and calcium channel blocker(RR=1.36,95%CI[0.91,2.03],P=0.14).(2)In terms of reducing headache frequency,when the unit of headache frequency was times per month,Yangxue Qingnao Granules combined with calcium channel blocker was better than calcium channel blocker(MD=-1.39,95%CI[-1.83,-0.95],P<0.00001),when the unit of headache frequency was times daily,Yangxue Qingnao Granules combined with calcium channel blocker was better than calcium channel blocker(MD=-2.08,95%CI[-2.34,-1.82],P<0.00001).(3)In terms of headache intensity,when headache intensity was scored by pain intensity,Yangxue Qingnao Granules combined with calcium channel blocker was better than calcium channel blocker(MD=-0.70,95%CI[-0.81,-0.59],P<0.00001),when headache intensity was scored by VAS score,Yangxue Qingnao Granules combined with calcium channel blocker was better than calcium channel blocker(MD=-1.59,95%CI[-2.13,-1.06],P<0.00001).(4)In terms of reducing headache duration,Yangxue Qingnao Granules combined with calcium channel blocker was better than calcium channel blocker(SMD=-3.13,95%CI[-4.12,-2.15],P<0.00001).GRADE system showed that the evidence level of the above outcome indicators was low and extremely low.Twelve cases of adverse reactions were reported,all of which were mild.The results showed that the combination of Yang-xue Qingnao Granules can improve the effective rate,reduce the headache frequency,the headache intensity and the headache duration,and had good safety and low incidence of adverse reactions compared with the single calcium channel blocker.However,there was no difference in the effective rate between Yangxue Qingnao Granules alone and calcium channel blocker.In view of the low quality of this study,which affects the reliability of the conclusion,it is necessary to use the conclusion of this study carefully,and more high-quality randomized controlled trials are needed to further verify in the future.