研究目的
本文以系统综述的方式探讨不同剂量新型口服抗凝药和华法林治疗 70 岁以上
老年房颤患者的有效性和安全性，为未来临床标准化用药提供有效的循证医学基础。
方法
从数据库建立到 2021 年 3 月，进行 PubMed、EMBASE、Cochrane Library、web
of science 等数据库检索，收集其中收录的公开发表的关于比较不同剂量 NOACs（达
比加群、利伐沙班、阿哌沙班、艾多沙班、西美加群）与华法林治疗 70 岁以上老
年非瓣膜性房颤患者比较的随机对照实验（RCT）或队列研究文献。由 2 名独立研
究者筛选文献并提取数据，使用 Stata15.0 软件进行荟萃分析。
结果
研究共纳入 18 篇随机对照实验，1 篇队列研究，共 215471 例患者。结果显示：
与华法林相比，低剂量（110mg）（OR=0.88，95%CI：0.79-0.98，P=0.02)和常规
剂量（150mg）（OR=0.67，95%CI：0.59-0.76，P<0.00001）达比加群均可降低 70
岁以上老年房颤患者卒中/系统性栓塞（SSE）发生率；常规剂量（OR=0.93，95%CI：
0.86-1.01，P=0.09)达比加群不降低严重出血发生率，但低剂量（OR=0.79，95%CI：
0.73-0.86，P=<0.00001)可显著降低严重出血风险；常规剂量（20mg）（OR=0.84，
95%CI：0.76-0.92，P=0.0004)利伐沙班显著降低 70 岁以上老年房颤患者卒中/SSE
发生率，而不增加严重出血发生率（OR=1.04，95%CI：0.97-1.12，P=0.25)；常规
剂量阿哌沙班（5mg）可显著降低 70 岁以上老年房颤患者卒中/SSE（OR=0.82，95%CI：
0.72-0.92，P=0.001）以及严重出血发生率（OR=0.70，95%CI：0.64-0.76，P<0.00001）；
常规剂量（36mg）（OR=0.93，95%CI：0.64-1.35，P=0.69）西美加群降低 70 岁以
上老年房颤患者卒中/SSE 发生率不亚于华法林，但显著降低严重出血风险（OR=0.76，
95%CI：0.62-0.92，P=0.006）。低剂量（15-30mg）（OR=1.14，95%CI：0.99-1.31，
P=0.08)和常规剂量（30-60mg）（OR=0.71，95%CI：0.43-1.17，P=0.18）艾多沙
班降低 70 岁以上老年房颤患者卒中/SSE 发生率不亚于华法林，但显著降低严重出
血风险（OR=0.42，95%CI：0.30-0.59，P=<0.00001)、（OR=0.73，95%CI：0.57-0.93，
P=0.01)。
结论
与华法林相比，NOACs 具有良好的抗凝效果。在严重出血方面，对于 70 岁以上
的老年房颤患者，除常规剂量达比加群严重出血风险增加，其他新型口服抗凝药，
无论是低剂量还是高剂量口服均是安全有效的。
关键词
Meta 分析；新型口服抗凝药；华法林；老年房颤

Objective
This paper systematically reviews the clinical benefits and risks of different new
oral anticoagulants and warfarin in the treatment of patients with atrial fibrillation over
70 years old, expecting to provide effective evidence-based medical basis for clinical
standardized drug use in the future.
Methods
From the construction of the database to March 2021, Pubmed, Embase, Cochrane
Library, Web of Science and other databases were searched. To collect published
randomized controlled or prospective cohort studies comparing NOACs (dabigatran,
rivaroxaban, Apisaban, Edoxaban, simegatran) with warfarin in the treatment of atrial
fibrillation in older adults 70 years of age or older. Two independent investigators
filtrated the documents and fetchded the information for a meta-analysis by using
Stata15.0 software.
Results
215471 patients in 18 RCTs and 1 PCS were brought into the study.The results
showed that compared with warfarin, low-dose (110mg) (OR = 0.88,95% CI: 0.79- 0.98,
P = 0.02), and standard-dose（150mg）（OR=0.67，95%CI：0.59-0.76，P<0.00001）
dabigatran reduced the risk of S/SSE in patients over 70 years old with atrial fibrillation；
Standard-dose dabigatran（OR=0.93，95%CI：0.86-1.01，P=0.09) did not decrease the
risk of major bleeding ，but Low-dose did it （OR=0.79，95%CI：0.73-0.86，P=<0.00001)；
Standard-dose（20mg）（OR=0.84，95%CI：0.76-0.92，P=0.0004) rivaroxaban could
considerably reduce the risk of stroke/ SSE in geriatric patients over 70 years old with
atrial fibrillation，not increase the risk of major bleeding（OR=1.04，95%CI：0.97-1.12，
P=0.25) ；Standard-dose（5mg）apixaban could considerably decrease the risk of stroke/
SSE（OR=0.82，95%CI：0.72-0.92，P=0.001） and major bleeding（OR=0.70，95%CI：
0.64-0.76 ， P<0.00001 ） in patients over 70 years old with atrial fibrillation ；
Standard-dose（36mg）（OR=0.93，95%CI：0.64-1.35，P=0.69）ximelagatran decreased
the incidence of stroke/ SSE in patients over 70 years old with atrial fibrillation as much
as warfarin, but could considerably decrease the risk of major bleeding （OR=0.76，95%CI：
0.62-0.92，P=0.006）.Low-dose（15-30mg）（OR=1.14，95%CI：0.99-1.31，P=0.08)
and standard-dose（30-60mg） （OR=0.71，95%CI：0.43-1.17，P=0.18）edoxaban
decreased the incidence of stroke/ SSE in patients over 70 years old with atrial
7
fibrillation as much as warfarin，but considerably decrease the risk of major bleeding
（OR=0.42，95%CI：0.30-0.59，P=<0.00001)、（OR=0.73，95%CI：0.57-0.93，P=0.01).
Conclusion
Compared with warfarin, NOACs has better anticoagulant effect. In terms of severe
bleeding, with the exception of conventional doses of dabigatran, the new oral
anticoagulants are safe and effective in both low and high oral doses for patients over 70
years of age with atrial fibrillation.
Key words
Meta-analysis, novel oral anticoagulant, Warfarin,Atrial fibrillation, elderly