直接口服抗凝药与华法林在有大出血史房颤患者中有效性和安全性的meta分析

Comparison of the efficacy and safety of direct oral anticoagulants with warfarin in atrial fibrillation patients with a history of major bleeding: a meta-analysis

目的 系统评价直接口服抗凝药(DOACs)与华法林治疗有大出血史的房颤患者有效性和安全性,为临床合理用药提供循证证据。方法 计算机检索PubMed、Cochrane Library、Embase、中国知网、万方数据库、维普数据库,检索时限从建库至2022年3月。收集其中已公开发表的关于DOACs(利伐沙班、达比加群、阿哌沙班、艾多沙班)与华法林在大出血史的房颤患者比较的文献。由2名研究员按照纳排标准独立筛选文献,提取资料并进行文献质量评价,采用Revman 5.3软件进行meta分析。结果 共纳入9项研究,共53 877例患者。Meta分析结果显示:在有效性方面,DOACs组比华法林组较少发生脑卒中或系统性栓塞的风险(OR=0.68,95%CI:0.48~0.96,P=0.03),且差异有统计学意义;在安全性方面,DOACs组比华法林组较少发生大出血的风险(OR=0.56,95%CI:0.41~0.78,P=0.0005)和全因死亡率(OR=0.54,95%CI:0.38~0.77,P=0.0007),且差异有统计学意义。进一步分析显示:DOACs组比华法林组较少发生脑卒中或系统性栓塞(OR=0.57,95%CI:0.38~0.86,P=0.008)、大出血(OR=0.53,95%CI:0.37~0.75,P=0.0004)和全因死亡的风险(OR=0.49,95%CI:0.31~0.77),P=0.002),且差异均有统计学意义;在欧美地区,两组脑卒中或系统性栓塞(OR=0.83,95%CI:0.65~1.07,P=0.16)、大出血(OR=0.72,95%CI:0.37~1.39,P=0.33)和全因死亡(OR=0.71,95%CI:0.48~1.04,P=0.08)的发生风险差异无统计学意义。结论 与华法林相比,DOACs在有大出血史的房颤患者中显示出更好的有效性和安全性,尤其是亚洲地区,但该研究需要更多随机对照试验来验证。

Objective To evaluate the efficacy and safety of direct oral anticoagulants and warfarin in the treatment of patients with atrial fibrillation with a history of major bleeding,and provide evidence-based evidence for clinical rational drug use. Methods PubMed,Cochrane Library,Embase,CNKI,Wanfang Database,and VIP database were searched,and the search time was from the establishment of the databases to March 2022. To collect published literature on the comparing of DOACs(rivaroxaban,dabigatran,apixaban,edoxaban)and warfarin in patients with atrial fibrillation with a history of major bleeding. Two researchers independently screened the literature according to the inclusion and exclusion criteria,then extracted the data and evaluated the quality of the literature. Revman 5. 3 software was used for meta-analysis. Results Nine studies with a total of 53 877 patients were included. Meta-analysis results showed that in terms of efficacy,the DOACs group had less risk of stroke/systemic embolism than the warfarin group(OR=0. 68,95%CI:0.48-0.96,P=0.03). In terms of safety,the DOACs group had statistically lower risk of major bleeding(OR=0. 56,95%CI:0.41-0.78),P=0.0005) and all-cause mortality(OR=0. 54,95%CI:0. 38-0. 77,P=0. 0007). Further analysis showed that DOACs group had less risk of stroke/systemic embolism(OR=0.57,95%CI:0.38-0. 86,P=0.008),major bleeding(OR=0.53,95%CI:0.37-0.75,P=0.0004) and allcause death(OR=0. 49,95%CI:0.31-0.77,P=0. 002) than warfarin group,and the difference were statistically significant. In Europe and the United States,there were no significant difference in the risk of stroke/systemic embolism(OR=0. 83,95%CI:0.65-1.07,P=0.16),major bleeding(OR=0.72,95%CI:0.37-1.39,P=0.33) and all-cause death(OR=0.71,95%CI:0. 48-1.04,P=0.08) between the two groups. Conclusion Compared with warfarin,DOACs show better efficacy and safety in patients with atrial fibrillation with a history of major bleeding,especially in the Asian region,but more randomized controlled trials are needed to validate this conclusion.