复方血栓通胶囊联合羟苯磺酸钙片治疗早期糖尿病视网膜病变疗效的Meta分析及试验序贯分析

目的系统评价复方血栓通胶囊联合羟苯磺酸钙片治疗早期糖尿病视网膜病变(DR)的临床疗效,为临床治疗提供参考。方法检索中国生物医学文献数据库(CBM)、中国知识资源总库(CNKI)、中国学术期刊数据库(万方数据)、中文科技期刊数据库(维普网)、PubMed、Embase、CochraneLibarary,收集试验组(复方血栓通胶囊联合羟苯磺酸钙片)与对照组(单用羟苯磺酸钙片)治疗早期DR的随机对照试验(RCT)。采用Cochrane5.1.0偏倚风险评估工具对纳入研究方法学质量进行评价,提取数据,并用RevMan5.2进行Meta分析。采用倒漏斗图法和Egger’s检验评估发表偏倚,采用TSA0.9软件对临床总有效率进行试验序贯分析。结果共纳入19项RCT,涉及患者1778例。试验组临床总有效率(RR=3.74,95%CI2.87,4.87],P<0.001)、临床复发率(RR=0.14,95%CI0.05,0.37],P=0.002)、视力(MD=0.12,95%CI0.09,0.15],P<0.001)、视野灰度值(MD=-1.01,95%CI-1.09,-0.93],P<0.001)、黄斑厚度(MD=-66.07,95%CI-74.10,-58.05],P<0.001)、血管瘤体积(MD=-3.27,95%CI-3.71,-2.84],P<0.001)、血管瘤数量(MD=-2.59,95%CI-3.05,-2.13],P<0.001)、出血斑点面积(MD=-0.93,95%CI-1.06,-0.80],P<0.001)均显著优于对照组(P<0.001),试验组动脉血流速度、hs-CRP、血糖、血液黏度、血清血管内皮生长因子、血清胰岛素样生长因子-1、中医症状积分改善程度均显著优于对照组(P<0.001)。漏斗图法和Egger’s线性回归分析提示不存在发表偏倚,敏感性分析提示结果稳定可信。2组患者均未见明显不良反应。试验序贯分析提示,复方血栓通胶囊联合羟苯磺酸钙片较单用羟苯磺酸钙片治疗早期DR疗效证据确切。结论复方血栓通胶囊联合羟苯磺酸钙片较单用羟苯磺酸钙片治疗早期DR疗效更佳,且未见明显不良反应。确切结论有待更多高质量、多中心、大规模的RCT证实。

Meta-analysis and Trial Sequential Analysis of Efficacy of Compound Xueshuantong Capsules Combined with Calcium Dobesilate Tablet in the Treatment of Early Diabetic Retinopathy

Objective To systematically review efficacy of compound Xueshuantong Capsules combined with calcium dobesilate tablet for early diabetic retinopathy(DR);To provide references for clinical treatment. Methods Chinese Biomedical Literature Database(CBM), China Knowledge Resources Database(CNKI), Chinese Academic Journals Database(Wanfang Data), Chinese Sci-tech Periodicals Database(VIP), PubMed, Embase, and Cochrane Libarary were retrieved. RCTs about experimental group(Compound Xueshuantong Capsules combined with calcium dobesilate tablet for early DR) and control group(calcium dobesilate tablet alone) were collected. Cochrane5.1.0 bias risk assessment tool was used to evaluate the methodological quality of the included studies, data were extracted, and Meta-analysis was performed with RevMan5.2. The inversion funnel chart method and Egger’s test were used to evaluate publication bias, and TSA 0.9 software was used to conduct trial sequential analysis of the total clinical effective. Results Totally of 19 RCTs were included, involving 1778 patients. Results of Meta-analysis showed the total clinical effective rate(RR=3.74, 95%CI 2.87, 4.87], P<0.001), the total clinical recurrence rate(RR=0.14, 95%CI 0.05, 0.37], P=0.002), vision(MD=0.12, 95%CI 0.09, 0.15], P<0.001), grayscale value of field of vision(MD=-1.01, 95%CI -1.09,-0.93], P<0.001), macular thickness(MD=-66.07, 95%CI -74.10,-58.05], P<0.001), the volume of hemangioma(MD=-3.27, 95%CI -3.71,-2.84], P<0.001), the number of hemangioma(MD=-2.59, 95%CI -3.05,-2.13], P<0.001), the area of hemorrhagic spot(MD=-0.93, 95%CI -1.06,-0.80], P<0.001) in the experimental group were better than those of the control group(P<0.05). Besides, the ocular arterial blood flow velocity, serum inflammatory factor hs-CRP, blood sugar level, blood viscosity, VEGF, IGF-1 and the TCM symptom score in the experimental group were better than those of the control group(P<0.05). Funnel plots and Egger’s linear regression showed that there was no publication bias. Sensitivity analysis showed that the results of this study were stable and reliable. No obvious adverse drug reactions were observed in all studies. Trail sequential analysis suggests that the evidence for the efficacy of Compound Xueshuantong Capsules combined with calcium dobesilate tablet is better than that of calcium dobesilate tablet alone for early DR. Conclusion The efficacy of Compound Xueshuantong Capsules combined with calcium dobesilate tablet is better than that of calcium dobesilate tablet alone for early DR, without obvious adverse reactions. The exact conclusions need to be confirmed by more high-quality, multi-center, large-scale RCTs.