摘要
目的 系统评价新型口服抗凝药（NOAC）治疗急性静脉血栓栓塞症（VTE）的疗效及出血风险. 方法 计算机检索有关数据库截至2017年12月收录的关于NOAC治疗VTE的随机对照试验（RCT）,筛选符合纳入标准的文献并进行质量评价,结局指标包括症状性VTE复发率、全因病死率、大出血发生率或临床相关性非重大（CRNM）出血发生率.应用STATA 13.1软件,采用网络Meta分析方法对符合纳入标准的研究结果进行合并,分析的效应指标为比值比（OR）及其95%置信区间（CI）. 结果 共9项RCT纳入本分析,包括27 827例患者,涉及利伐沙班、阿哌沙班、依度沙班、达比加群酯和华法林等5种抗凝药物.质量评价结果显示,9项RCT中4项为低偏倚风险,2项为偏倚风险不确定,3项为高偏倚风险.网络 Meta分析结果显示,应用5种不同抗凝药物的急性VTE患者之间症状性VTE复发率和全因病死率的差异均无统计学意义;累积排序概率曲线下面积（SUCRA）分析结果显示,在降低症状性VTE复发率及全因病死率方面,阿哌沙班（SUCRA：69.0%, 77.1%）疗效最优的概率最高,其次为利伐沙班（SUCRA：60.7%,51.4%）.在安全性方面,阿哌沙班致大出血的风险显著低于达比加群酯和依度沙班（达比加群酯比阿哌沙班：OR ＝2.36,95%CI：1.16-4.83;依度沙班比阿哌沙班：OR＝2.64,95%CI：1.36-5.13）;阿哌沙班致CRNM出血风险显著低于依度沙班和利伐沙班（依度沙班比阿哌沙班：OR＝1.67,95%CI：1.26-2.20;利伐沙班比阿哌沙班,OR＝2.09,95%CI：1.59-2.74）;达比加群酯致CRNM出血风险显著低于依度沙班和利伐沙班（依度沙班比达比加群酯：OR＝1.36,95%CI：1.01-1.84;利伐沙班比达比加群酯：OR＝1.71,95%CI：1.27-2.30）.出血风险的SUCRA分析结果显示,阿哌沙班致大出血的风险（SUCRA：98.2%）可能最低,其次为利伐沙班、达比加群酯、依度沙班、华法林.阿哌沙班致CRNM出血的风险（SUCRA：97.0%）最低,其次为达比加群酯、依度沙班、利伐沙班、华法林. 结论 对于新发或复发的急性VTE成年患者,各NOAC与华法林疗效相似,出血风险多显著低于华法林,其中阿哌沙班疗效最佳、出血风险最低的概率最大.
Objective To systematically evaluate the efficacy and bleeding risk of new oral anticoagulants （NOAC）in treatment for acute venous thromboembolism （VTE）. Methods Randomized controlled trials （RCT）about NOAC treatment for VTE in related databases collected up to December 2017 were searched. The literature in accordance with the inclusion criteria were selected and evaluated. The outcome measures included recurrence rate of VTE,all-cause mortality,incidence of hemorrhea or incidence of clinically relevant non-major （CRNM）bleeding. The results of RCT in accordance with inclusion criteria were combined using network meta-analysis. The effect measures were expressed in odds ratio （OR）with its corresponding 95% confidence interval （CI）. Results A total of 9 RCT comprising 27 827 patients and 5 anticoagulant drugs （rivaroxaban,apixaban,edoxaban,dabigatran,and warfarin）were enrolled in the study. The quality evaluation showed that 4 of 9 RCT＇s bias risks were low,2 were uncertain,and 3 were high. Network meta-analysis results showed that neither the differences of recurrence rate of symptomatic VTE nor that of all-cause mortality among the patients with acute VTE using 5 different anticoagulant drugs were statistically significant. The results of surface under the cumulative ranking probability （SUCRA） showed that apixaban had the highest probability of having the optimal curative effect in decreasing symptomatic recurrence rate and all-cause mortality （SUCRA：69.0%,77.1%）,followed by rivaroxaban （SUCRA：60.7%,51.4%）. About the safety of the drugs,the risk of hemorrhoea induced by apixaban was lower than that induced by dabigatran and edoxaban （dabigatran vs. apixaban,OR=2.36,95%CI：1.16-4.83;edoxaban vs. apixaban,OR=2.64,95%CI：1.36-5.13）. The risk of CRNM bleeding associated with apixaban was lower than that associated with rivaroxaban and edoxaban （edoxaban vs. apixaban,OR =1.67,95%CI：1.26-2.20;rivaroxaban vs. apixaban,OR =2.09,95%CI：1.59-2.74）. The risk of CRNM bleeding associated with dabigatran was lower than that due to edoxaban and rivaroxaban （edoxaban vs. dabigatran, OR=1.36,95%CI：1.01-1.84;rivaroxaban vs. dabigatran,OR =1.71,95%CI：1.27-2.30）. The results of SUCRA showed that the probability of hemorrhoea induced by apixaban was the lowest （SUCRA：98.2%）,followed by rivaroxaban,dabigatran,edoxaban,and warfarin;the probability of CRNM bleeding induced by apixaban was the lowest （97.0%）,then followed by dabigatran,edoxaban,rivaroxaban,and warfarin. Conclusions For adult patients with new-onset or relapsed acute VTE,the efficacy of NOAC and warfarin were similar. The risk of bleeding with NOAC treatment was significantly lower than that with warfarin,of which,apixaban had the highest probability of having the best efficacy and the lowest risk of bleeding.
作者
李婷
封宇飞
倪倩
周得平
Li Ting;Feng Yufei;Ni Qian;Zhou Deping(Department of Pharmacy,Belting Hospital,National Center of Gerontology,Assessment of Clinical Drugs Risk and Individual Application Key Laboratory,Beijing 100730,China)
出处
《药物不良反应杂志》
CSCD
2018年第4期249-258,共10页
Adverse Drug Reactions Journal
关键词
抗凝药
口服
静脉血栓栓塞
出血
网络meta分析
Anticoagulants
oral administration
Venous thromboembolism
Hemorrhage
Network meta-analysis
