基于贝叶斯网状Meta分析的丹参类注射剂治疗心脑血管疾病临床评价研究

发布时间：2018-01-11 14:29

本文关键词：基于贝叶斯网状Meta分析的丹参类注射剂治疗心脑血管疾病临床评价研究　出处：《北京中医药大学》2017年硕士论文　论文类型：学位论文

【摘要】：研究背景据世卫组织统计,心脑血管疾病的发病率逐年升高,已成为导致人类死亡的首要原因。近年来,中药注射剂在心脑血管疾病中发挥了不可替代的作用,特别是丹参类注射剂,具有较好的经济效益和社会效益。临床实践中,医务工作者经常需要从丹参类注射剂中选择出疗效较好的品种,然而丹参类注射剂间缺乏直接对比的随机试验,且经典Meta分析因其局限性无法实现多品种间的综合比较分析。故而,探索应用新的研究方法综合评价不同品种丹参类注射剂治疗心脑血管疾病的疗效,具有重要学术意义和临床价值。正基于此,本研究以急性脑梗死、不稳定型心绞痛为切入点,应用Meta分析、网状Meta分析等方法,对丹参类注射剂的有效性和安全性开展横向综合评价,促进临床合理用药。研究目的运用网状Meta分析方法评价丹参类注射剂治疗急性脑梗死、不稳定型心绞痛的有效性和安全性。研究方法1.网状Meta分析基于贝叶斯理论,运用WinBUGS软件对数据进行分析,运用Stata13.0软件对结果进行可视化,绘制曲线下面积图,预测治疗措施疗效排序。计算不一致因子(IF)及其95%CI评价一致性。2.Meta分析全面、系统检索国内外中、英文数据库,收集相关的临床随机对照试验(RCTs)。质量评价采用偏倚风险评价工具。运用RevMan软件、Stata软件进行数据分析。3.文献研究法采用文献研究的方法对检索到的文献资料进行统计分析,包括对丹参类注射剂基本功效、适应症、安全性和对已发表的丹参类注射剂系统评价现状进行统计分析。研究结果(1)丹参类注射剂治疗急性脑梗死研究结果对于急性脑梗死,共检索到10007篇文献,经筛查后,最终纳入157个RCT,15570例受试者,所有研究都是二臂RCT,所有患者均诊断为急性脑梗死。纳入干预措施包括丹参注射剂、复方丹参注射剂、丹红注射剂、丹参川芎嗪注射剂、丹参酮ⅡA磺酸钠注射剂、丹参多酚酸盐注射剂、丹参多酚酸注射剂、冠心宁注射剂。所有研究均提及"随机分组",29个研究通过"随机数字表"产生随机序列,11个研究提及盲法,2个研究有不完整结局,其他研究均无失访或撤出病例。所有纳入研究未获得提前发布的试验方案,可能存在选择性报告。133个研究报告了临床疗效总有效率,112个研究报告了神经功能缺损,31个研究报告了日常生活活动能力评分,24个研究报告了全血高切黏度,24个研究报告了全血低切黏度,25个研究报告了血浆黏度,27个研究报告了纤维蛋白原。Meta分析结果显示:对于急性脑梗死患者,丹参类注射剂能提高临床疗效总有效率,改善神经功能缺损、提高日常生活活动能力。网状Meta分析结果显示:在提高临床疗效总有效率方面,冠心宁注射剂排序最佳,但因纳入数量仅有1项,研究结果无法确证;在改善神经功能缺损、日常生活活动能力、全血低切黏度、全血高切黏度方面,丹参酮ⅡA磺酸钠注射剂效果排序最佳;在降低血浆黏度方面,丹红注射剂效果排序最佳;在降低纤维蛋白原方面,丹参多酚酸注射剂效果排序最佳。25个研究共报道70例不良反应/不良事件。主要表现为头痛、头晕、皮肤瘙痒、恶心、呕吐、皮疹、滴注侧肢体皮肤红肿等。(2)丹参类注射剂治疗不稳定型心绞痛研究结果对于不稳定型心绞痛,共检索到3966篇文献,经筛查后,最终纳入172 RCTs,16306例受试者,所有纳入研究都是二臂研究,所有患者均诊断为不稳定型心绞痛。纳入干预措施包括丹参注射剂、复方丹参注射剂、丹红注射剂、丹参川芎嗪注射剂、丹参酮ⅡA磺酸钠注射剂、丹参多酚酸盐注射剂、丹参多酚酸注射剂、冠心宁注射剂。所有研究均提及"随机分组",20个研究通过"随机数字表"产生随机序列,7个研究采用盲法,均未提及分配隐藏,所有研究均无失访或撤出病例。所有纳入研究未获得提前发布的试验方案,可能存在选择性报告。5个研究报告了心血管事件,8个研究报告了硝酸甘油用量,18个研究报告了心绞痛发作频率,15个研究报告了心绞痛发作持续时间,172个研究报告了心绞痛疗效,108个研究报告了心电图疗效,32个研究报告了总胆固醇,31个研究报告了甘油三酯,23个研究报告了高密度脂蛋白,27个研究报告了低密度脂蛋白。Meta分析结果显示:丹参类注射剂治疗不稳定型心绞痛在提高心绞痛疗效、心电图疗效,减少心血管事件、硝酸甘油用量、心绞痛发作频率、心绞痛发作持续时间、改善血脂方面有一定的疗效。因原始研究大多数未提及心血管事件、硝酸甘油用量、心绞痛发作频率、心绞痛发作持续时间,无法构建证据网络,故仅对心绞痛疗效、心电图疗效、血脂指标进行网状Meta分析。网状Meta分析结果显示:在提高心绞痛疗效方面,丹参酮ⅡA磺酸钠注射剂效果排序最佳;在提高心电图疗效方面,丹参酮ⅡA磺酸钠注射剂效果排序最佳;在改善TC方面,丹参多酚酸盐注射剂效果排序最佳;在改善TG方面,丹红注射剂效果排序最佳;在改善HDL-C方面,丹参注射剂效果排序最佳;在改善LDL-C方面,丹参多酚酸盐注射剂效果排序最佳。32个研究共报道117例不良反应/不良事件。主要表现为头痛、头晕、腹痛、恶心、呕吐、皮肤瘙痒、皮肤点片状出血点等。研究结论在西医常规治疗的基础上,联合使用丹参类注射剂可以提高急性脑梗死、不稳定型心绞痛的治疗效果。网状Meta分析结果提示冠心宁注射剂在提高急性脑梗死患者临床疗效方面较好,丹参酮ⅡA磺酸钠注射剂在改善急性脑梗死患者神经功能缺损、日常生活活动能力、全面低切黏度、全血高切黏度方面效果较好,在提高不稳定型心绞痛患者的心绞痛疗效和心电图疗效方面较好;丹红注射剂在降低急性脑梗死患者血浆黏度、改善不稳定型心绞痛患者甘油三酯方面较好;丹参多酚酸盐注射剂在改善不稳定型心绞痛患者总胆固醇、低密度脂蛋白方面较好;丹参多酚酸注射剂在降低急性脑梗死患者纤维蛋白原方面效果较好。对于丹参类注射剂的安全性,因纳入研究安全性不一,不能得出明确的结论,仍需进一步探讨。今后应开展更多设计严谨的随机双盲对照试验对丹参类注射剂的疗效与安全性作进一步评价。
[Abstract]:According to the research background of the World Health Organization statistics, cardiovascular disease incidence increased year by year, has become the leading cause of human death. In recent years, Chinese medicine injection has played an irreplaceable role in cardiovascular diseases, especially Danshen injection, with good economic and social benefits. In clinical practice, medical workers often need to choose a good effect from the varieties of Radix Salviae miltiorrhizae injection, Salvia miltiorrhiza injection but lack of randomized trials directly comparing, and the classic Meta analysis can not be achieved due to the limitation of multi varieties comparative analysis. Therefore, to explore the effect of application of new research methods of comprehensive evaluation of different varieties of Radix Salviae Miltiorrhizae Injection in treatment of cardiovascular and cerebrovascular the disease, has important academic significance and clinical value. Based on this, in this study, acute cerebral infarction, unstable angina as the starting point, the application of Meta Network analysis, Meta analysis and other methods, to carry out comprehensive evaluation of transverse efficacy and safety of Salvia miltiorrhiza injection, promote clinical rational drug use. Research using Meta mesh analysis method for evaluation of Danshen injection in treatment of acute cerebral infarction, efficacy and safety of unstable angina pectoris. Methods 1. Meta mesh based on Bayesian theory and use WinBUGS to analyze the data, using Stata13.0 software to visualize the results, draw the area under the curve graph, prediction of treatment efficacy. Sort of inconsistent calculation factor (IF) and 95% CI evaluation of consistency of.2.Meta comprehensive analysis, retrieval system at home and abroad, English database, collection of Clinical RCTs (RCTs). Quality evaluation using bias risk assessment tool. Using RevMan software, data analysis methods.3. literature research by literature research by Stata software Statistical analysis of the retrieved documents, including the basic effect of Radix Salviae miltiorrhizae injection, indications, safety and statistical analysis of Radix Salviae Miltiorrhizae Injection status evaluation system. The research results have been published (1) Danshen injection in treatment of acute cerebral infarction results in acute cerebral infarction and 10007 literatures were retrieved and screened after a total of 157 RCT, 15570 subjects, all two arm RCT, all patients were diagnosed with acute cerebral infarction. Included interventions including Danshen injection, compound Danshen injection, Danhong injection, Danshen ligustrazine injection of sodium tanshinone A sulfonate injection, salvianolate injection, Salvia miltiorrhiza polyphenol acid injection, injection of Guanxinning. All studies are mentioned "randomized", 29 research through the "random number table" to generate random sequence, 11 studies mentioned blind method, 2 Research Incomplete ending, other studies were not lost or withdraw cases. All included studies did not obtain the test plan released in advance, there may be a selective report.133 study reported the total curative rate, 112 research reports of neurologic impairment, 31 Research Report ADL score, 24 research report the whole blood viscosity, 24 studies reported low blood viscosity, plasma viscosity in 25 studies, 27 studies reported the fibrinogen.Meta analysis results showed that: for patients with acute cerebral infarction, Danshen injection can improve the clinical curative effect of the total efficiency, improve neurological function, improve the ability of daily life net. Meta analysis results showed that: in improving clinical curative effect the total efficiency, but the best sort of Guanxinning Injection, into the number of only 1, the results can not be confirmed in the improvement of God; The function defect and activities of daily living, low blood viscosity, high blood viscosity, tanshinone II A sodium sulfonate injection in reducing the effect of ranking the best; plasma viscosity, the effect of Danhong injection in the best order; decrease fibrinogen, Danshen phenolic acid injection effect of multi sort optimal.25 studies were reported adverse 70 cases of adverse reaction / event. The main manifestations are headache, dizziness, skin itching, nausea, vomiting, rash, drip limbs skin redness. (2) Danshen injection in treatment of unstable angina pectoris results for unstable angina, a total of 3966 articles were retrieved, after screening, the final in 172 RCTs, 16306 subjects, all included in the study are two arm study, all patients were diagnosed with unstable angina pectoris. Included interventions including Danshen injection, compound Danshen injection, Danhong injection, Salvia miltiorrhiza Ligustrazine injection of sodium tanshinone A sulfonate injection of salvianolate injection, salvianolate injection, injection of Guanxinning. All studies are mentioned "randomized", 20 research through the "random number table" to generate random sequence, 7 studies using blind method, were not mentioned allocation concealment, all of all lost or withdrawn. All cases included in the study did not obtain the test plan released in advance, there may be a selective report.5 study reported cardiovascular events, 8 studies reported on the dosage of nitroglycerin, 18 studies reported the frequency of angina attack, 15 studies reported on the duration of angina pectoris, 172 Research Report angina pectoris, 108 research report the EKG, 32 studies reported total cholesterol, 31 studies reported in 23 studies of triglycerides, high density lipoprotein, 27 studies reported low Density lipoprotein.Meta analysis results showed that Danshen injection in treatment of unstable angina pectoris in improving angina pectoris, ECG curative effect, reduce cardiovascular events, the dosage of nitroglycerin, angina frequency, duration of angina pectoris have certain curative effect, improve blood pressure. Because of the original study did not mention the most cardiovascular events, nitrate glycerol, angina frequency, duration of angina pectoris, unable to construct evidence network, so only on angina pectoris, ECG, blood lipid indexes were analyzed. The mesh network Meta Meta analysis results showed that: in the aspect of improving the efficacy of angina pectoris, sodium tanshinone A sulfonate injection effect in improving the ranking best; electrocardiogram effect of sodium tanshinone A sulfonate injection effect in improving the ranking best; TC, salvianolate injection effect in improving TG ranking the best; Dan. The effect of injection of red ranking best; in the improvement of HDL-C, ranking the best effect of Danshen injection in improving; LDL-C, salvianolate injection effect.32 studies were the best sort of reports of adverse reactions / 117 cases of adverse events. The main manifestations are headache, dizziness, abdominal pain, nausea, vomiting, skin itching, skin patchy bleeding the conclusion of the study. On the basis of conventional treatment, the combined use of Danshen injection can improve the acute cerebral infarction, unstable angina treatment. Meta analysis showed that the Guanxinning Injection mesh to improve the good clinical curative effect in patients with acute cerebral infarction, tanshinone II A sodium sulfonate injection in improving nerve function of acute cerebral infarction patients with defect. The activities of daily living, overall low shear viscosity, whole blood viscosity has better effect in improving the patients with unstable angina pectoris angina Curative effect and electrocardiogram efficacy; Danhong injection in reducing plasma viscosity in patients with acute cerebral infarction, improve unstable angina patients better triglyceride; salvianolate injection unstable angina in patients with total cholesterol, low density lipoprotein is better; salvianolic acid injection on acute cerebral infarction patients better reduce the fiber protein the original effect. For the safety of Danshen injection, because safety is not included in the study, no clear conclusion, still need further discussion. We should carry out more rigorous randomized double-blind design for further evaluation of control efficacy and safety test of Radix Salviae miltiorrhizae injection.

【学位授予单位】：北京中医药大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R259

【参考文献】