DataSheet1_Efficacy and safety of traditional Chinese medicine for intracranial hemorrhage by promoting blood circulation and removing blood stasis: A systematic review and meta-analysis of randomized controlled trials.docx

Background: Although blood-activating Chinese medicine (BACM) has been reported as adjuvant therapy for intracranial hemorrhage (ICH) in China, high-quality evidence is still lacking. Our study aimed to collect the latest high-quality randomized controlled trials (RCTs) and to evaluate the efficacy and safety of BACM for ICH.Methods: RCTs published between January 2015 and March 2022 were searched in databases, including China National Knowledge Infrastructure (CNKI), China Science and Technology Journal Database (VIP), Sino-Med, Wanfang, PubMed, Web of Science, Cochrane Library, and Embase without language restrictions. Eligible RCTs were included and both primary (clinical efficacy evidenced by decreased neurological deficit scores) and secondary outcomes (increased Barthel index, decreased NIHSS, hematoma volume, the volume of cerebral edema, the incidence of side effects, and mortality) were analyzed. The quality of included RCTs was assessed using the Cochrane risk of bias tool. In the meta-analysis, the pooled results were analyzed using Review Manager 5.3 and STATA14.0. Finally, The GRADEpro GDT software (Guideline Development Tool) was used to summarize the results. Sensitivity and subgroup analyses were conducted based on the follow-up time.Results: Fifteen RCTs, involving 1,579 participants, were included for analysis in our study. The pooled outcomes indicated that BACM combined with western medicine treatment (WMT) was superior to WMT alone for patients with ICH, demonstrated by the improvements in efficacy (RR = 1.22 (95% CI, [1.13 to 1.32], p < 0.001), neurological functions (MDNIHSS = −2.75, 95% CI [−3.74 to −1.76], p < 0.001), and activities of daily living (MDBarthel index = 5.95, 95% CI [3.92 to 7.98], p < 0.001), as well as decreased cerebral hematoma, cerebral edema (MD cerebral hematoma = −2.94, 95% CI [−3.50 to −2.37, p < 0.001 and MDcerebral edema = −2.66, 95% CI [−2.95 to −2.37], p < 0.001), side effects and mortality (RR = 0.84 (95% CI [0.60 to 1.19], p = 0.330 and RR = 0.51 (95% CI, [0.16 to 1.65], p = 0.260). In addition, Conioselinum anthriscoides “Chuanxiong” [Apiaceae], Camellia reticulata Lindl. [Theaceae], and Bupleurum sibiricum var. jeholense (Nakai) C.D.Chu [Apiaceae]) were the most frequently used herbs in the treatment of ICH. Recently, there was a trend toward the extensive use of another two herbs, including Rheum palmatum L. [Polygonaceae], Astragalus mongholicus Bunge [Fabaceae]) for ICH.Conclusion: BACM combined with WMT seems to be superior to WMT alone for patients with ICH. Further high-quality RCTs are warranted to confirm the efficacy and safety of BACM.

背景：尽管在中国，血液活化中药（BACM）已被报道为颅内出血（ICH）的辅助治疗手段，但高质量的证据仍然不足。本研究旨在收集最新的高质量随机对照试验（RCTs），并评估BACM对ICH的疗效与安全性。方法：在包括中国知网（CNKI）、中国科技期刊数据库（VIP）、Sino-Med、万方、PubMed、Web of Science、Cochrane Library和Embase在内的数据库中，检索了2015年1月至2022年3月期间发表的RCTs，检索范围不受语言限制。纳入符合条件的研究，并分析了主要结局（通过降低神经功能缺损评分证实的临床疗效）和次要结局（Barthel指数的提高、NIHSS评分的降低、血肿体积、脑水肿体积、副作用发生率及死亡率）。使用Cochrane偏倚风险工具评估纳入RCTs的质量。在荟萃分析中，使用Review Manager 5.3和STATA14.0软件对合并结果进行分析。最后，采用GRADEpro GDT软件（指南开发工具）总结结果。根据随访时间进行了敏感性分析和亚组分析。结果：本研究纳入了15项RCTs，涉及1579名参与者。合并结果提示，BACM联合西医治疗（WMT）对于ICH患者优于单独WMT，这一结论由以下改善得到证实：疗效（相对风险RR = 1.22，95%置信区间[1.13至1.32]，p < 0.001）、神经功能（MDNIHSS = −2.75，95%置信区间[−3.74至−1.76]，p < 0.001）和日常生活活动能力（MDBarthel指数 = 5.95，95%置信区间[3.92至7.98]，p < 0.001），以及降低脑血肿、脑水肿（MD脑血肿 = −2.94，95%置信区间[−3.50至−2.37]，p < 0.001和MD脑水肿 = −2.66，95%置信区间[−2.95至−2.37]，p < 0.001）、副作用和死亡率（相对风险RR = 0.84，95%置信区间[0.60至1.19]，p = 0.330和RR = 0.51，95%置信区间[0.16至1.65]，p = 0.260）。此外，白芷（Conioselinum anthriscoides “Chuanxiong”，伞形科）、红梅（Camellia reticulata Lindl.，山茶科）和北柴胡（Bupleurum sibiricum var. jeholense Nakai C.D.Chu，伞形科）是最常用于ICH治疗的中药材。最近，还有两种中药材的使用趋势逐渐扩大，包括掌叶大黄（Rheum palmatum L.，蓼科）和蒙古黄芪（Astragalus mongholicus Bunge，豆科）。结论：BACM联合WMT似乎优于单独WMT，对于ICH患者而言。为进一步证实BACM的疗效与安全性，尚需进行更多高质量RCTs。