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用于阿司匹林抵抗的中草药:一项系统评价与荟萃分析

Chinese Herbal Medicine for Aspirin Resistance: A Systematic Review and Meta-Analysis.

作者信息

Chen Hanyu, Shen Zhengjie, Chen Jiandong, Zhang Haowen, Chen Xiaohu

机构信息

First Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing, China.

Department of Cardiology, Jiangsu Province Hospital of Traditional Chinese Medicine, the Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China.

出版信息

PLoS One. 2016 May 6;11(5):e0154897. doi: 10.1371/journal.pone.0154897. eCollection 2016.

Abstract

OBJECTIVES

To assess the effectiveness and safety of Chinese herbal medicine (CHM) for the treatment of aspirin resistance (AR).

METHODS

A comprehensive research of seven electronic databases was performed for comparative studies evaluating CHM for AR. Two authors independently extracted data and assessed the methodological quality of the included trials using the Cochrane risk of bias tool. Data wasere synthesized by using RevMan 5.3 software. (PROSPERO Registration #CRD42015020182).

RESULTS

18 randomized controlled trials (RCTs) involving 1,460 patients were included. 15 RCTs reported significant difference in the reduction of platelet aggregation rate (PAR) induced by adenosine diphosphate (ADP) (P<0.05), and 11 reported significant effect of CHM plus aspirin to reduce PAR induced by arachidonic acid (AA) (P<0.05) compared with aspirin 100mg/d treatment. The pooling data of 3 RCTs showed the thromboxane B2 (TXB2) in patients with CHM plus aspirin versus aspirin were significantly reduced (Random Effect model (RE), Standard Deviation (SD) = -95.93, 95% Confidential Interval (CI)[-118.25,-73.61], P<0.00001). Subgroup analysis showed that TXB2 (Fixed Effect model (FE), SD = -89.23, 95%CI[-121.96,-56.49], P<0.00001) had significant difference in Tongxinluo capsule plus aspirin versus aspirin. 2 RCTs reported the clinical effective rate, and the meta-analysis result showed a significant difference in intervention and control group (FE, Relative Risk (RR) = 1.67, 95%CI[1.15, 2.42], P = 0.007<0.05). In 4 trials, CHM plus aspirin had better effects of reducing the reoccurrence of cerebral infarction than aspirin (FE, RR = 0.24, 95%CI [0.11, 0.49], P<0.0001). And one trial showed that CHM plus aspirin could decrease the National Institutes of Health Stroke Scale (NHISS) score (P<0.05) and increase the Barthel Index (BI) score (P<0.05). 4 trials stated that there were no adverse effects occurred in intervention group, and analysis showed significant difference of CHM or CHM plus aspirin in reducing the occurrence of adverse events (FE, RR = 0.22, 95%CI[0.13, 0.39], P<0.00001). 5 trials claimed that the CHM monotherapy and CHM adjunctive therapy for AR did not add the risk of bleeding (FE, RR = 0.50, 95%CI[0.20, 1.22], P = 0.13>0.05).

CONCLUSIONS

CHM may be effective and safe as an alternative and collaborative therapy for AR. However, the current evidence and potential promising findings should be interpreted with caution due to poor and varying methodological quality of included studies and the heterogeneity of interventions. Thus, further exploration of this strategy with adequately powered RCTs is warranted.

摘要

目的

评估中药治疗阿司匹林抵抗(AR)的有效性和安全性。

方法

对七个电子数据库进行全面检索,以查找评估中药治疗AR的比较研究。两位作者独立提取数据,并使用Cochrane偏倚风险工具评估纳入试验的方法学质量。使用RevMan 5.3软件进行数据合成。(国际前瞻性系统评价注册库注册号#CRD42015020182)。

结果

纳入18项随机对照试验(RCT),涉及1460例患者。15项RCT报告,与每日服用100mg阿司匹林治疗相比,中药在降低二磷酸腺苷(ADP)诱导的血小板聚集率(PAR)方面有显著差异(P<0.05);11项报告称,中药联合阿司匹林在降低花生四烯酸(AA)诱导的PAR方面有显著效果(P<0.05)。3项RCT的汇总数据显示,中药联合阿司匹林组患者的血栓素B2(TXB2)水平与阿司匹林组相比显著降低(随机效应模型(RE),标准差(SD)=-95.93,95%置信区间(CI)[-118.25,-73.61],P<0.00001)。亚组分析显示,通心络胶囊联合阿司匹林组与阿司匹林组相比,TXB2水平有显著差异(固定效应模型(FE),SD=-89.23,95%CI[-121.96,-56.49],P<0.00001)。2项RCT报告了临床有效率,荟萃分析结果显示干预组和对照组有显著差异(FE,相对危险度(RR)=1.67,95%CI[1.15,2.42],P=0.007<0.05)。在4项试验中,中药联合阿司匹林在降低脑梗死复发率方面比阿司匹林效果更好(FE,RR=0.24,95%CI[0.11,0.49],P<0.0001)。一项试验表明,中药联合阿司匹林可降低美国国立卫生研究院卒中量表(NHISS)评分(P<0.05),并提高巴氏指数(BI)评分(P<0.05)。4项试验表明干预组未发生不良反应,分析显示中药或中药联合阿司匹林在降低不良事件发生率方面有显著差异(FE,RR=0.22,95%CI[0.13,0.39],P<0.00001)。5项试验称,中药单药治疗和辅助治疗AR不会增加出血风险(FE,RR=0.50,95%CI[0.20,1.22],P=0.13>0.05)。

结论

中药作为AR的替代和联合治疗可能有效且安全。然而,由于纳入研究的方法学质量较差且存在差异,以及干预措施的异质性,目前的证据和潜在的有前景的发现应谨慎解读。因此,有必要通过足够样本量的RCT对该策略进行进一步探索。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2539/4859478/a99c8d402f35/pone.0154897.g001.jpg

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