摘要
目的:系统评价对新型冠状病毒感染疾病(Coronavirus Disease 2019,COVID-19)患者进行抗凝干预的有效性及安全性。方法:在PubMed、Embase、Cochrane Library、Clinical Trials、中国知网、万方和维普等数据库中检索国内外公开发表的关于COVID-19患者接受抗凝干预有效性和安全性的随机对照试验文献,提取资料并评价质量,对纳入文献采用RevMan 5.3软件进行Meta分析。结果:共纳入26篇文献,合计16 048例患者。结果显示,对于COVID-19门诊患者,预防剂量抗凝组与安慰剂或标准护理组在全因死亡率、全因住院率及血栓发生率方面均差异无统计学意义,但预防剂量抗凝组的非严重临床相关出血发生率高于安慰剂或标准护理组(RR=3.04,95%CI:1.33~6.90;P=0.008)。对于COVID-19住院患者,治疗剂量抗凝组静脉血栓栓塞(venous thromboembolism,VTE)发生率(RR=0.58,95%CI:0.44~0.77;P=0.000 1)、肺栓塞(pulmonary embolism,PE)发生率[RR=0.50,95%CI 0.36~0.69;P<0.01]及深静脉血栓(deep vein thrombosis,DVT)发生率(RR=0.68,95%CI:0.49~0.95;P=0.02)均低于中等/标准预防剂量抗凝组,但严重出血发生率(RR=1.88,95%CI:1.32~2.68;P=0.000 5)及非严重临床相关出血发生率(RR=3.21,95%CI:1.77~5.81;P=0.000 1)均高于中等/标准预防剂量抗凝组。亚组分析显示,对于基线D-二聚体≥2倍上限的COVID-19住院患者,治疗剂量抗凝组VTE、PE和DVT发生率均低于中等/标准预防剂量抗凝组,且不增加严重出血发生率;对于基线D-二聚体<2倍上限的COVID-19住院患者,治疗剂量抗凝组较中等/标准预防剂量抗凝组增加严重出血发生率,其他血栓指标疗效相当。结论:对于COVID-19门诊患者,预防抗凝治疗并不能降低血栓发生率,相反会增加非严重出血发生率,因此不建议预防性抗凝治疗。对于COVID-19住院患者,当基线D-二聚体≥2倍上限时,建议优先选择治疗剂量抗凝;当基线D-二聚体<2倍上限时,建议优先选择中等/标准预防剂量抗凝。
OBJECTIVE To systematically evaluate the efficacy and safety of anticoagulation interventions in Coronavirus Disease 2019(COVID-19)patients.METHODS Randomized controlled trials(RCTs)on the efficacy and safety of anticoagula-tion interventions in COVID-19 patients published at home and abroad were retrieved from databases such as PubMed,Embase,Cochrane Library,Clinical Trials,China National Knowledge Infrastructure(CNKI),Wanfang,and VIP.Data were extracted and the quality was evaluated.Meta-analysis was performed on the included literatures using RevMan 5.3 software.RESULTS A total of 26 literatures were included,involving 16 048 COVID-19 patients in total.The results of Meta-analysis showed no sig-nificant differences in the all-cause hospitalization rate,all-cause mortality rate and thrombotic rate in COVID-19 outpatients of prophylactic-dose anticoagulation treatment group and placebo or standard care group.However,the incidence of non-serious clinically relevant bleeding in the prophylactic-dose anticoagulation treatment group was significantly higher than that in the pla-cebo or standard care group(RR=3.04,95%CI:1.33-6.90;P=0.008).For COVID-19 hospitalized patients,the incidence of venous thromboembolism(VTE)(RR=0.58,95%CI:0.44-0.77;P=0.000 1),the incidence of pulmonary embolism(PE)(RR=0.50,95%CI:0.36-0.69;P<0.01),and the incidence of deep vein thrombosis(DVT)(RR=0.68,95%CI:0.49-0.95;P=0.02)in the therapeutic-dose anticoagulation group were significantly lower than those in the intermediate/standard prophylactic-dose anticoagulation group.However,both the incidence of serious bleeding(RR=1.88,95%CI:1.32-2.68;P=0.000 5)and the incidence of non-serious clinically relevant bleeding(RR=3.21,95%CI:1.77-5.81;P=0.000 1)were signifi-cantly higher than those in the intermediate/standard prophylactic-dose anticoagulation group.For COVID-19 hospitalized patients with a baseline D-dimer level≥2 times the upper limit,the incidences of VTE,PE,and DVT in the therapeutic-dose anticoagulation group were significantly lower than those in the intermediate/standard prophylactic-dose anticoagulation group,and there was no increase in the incidence of serious bleeding.For COVID-19 hospitalized patients with a baseline D-dimer level<2 times the upper limit,the incidence of serious bleeding in the therapeutic-dose anticoagulation group was significantly higher than that in the intermediate/standard prophylactic-dose anticoagulation group,while the efficacy in the thrombosis indica-tors was equivalent.CONCLUSION For COVID-19 outpatient patients,prophylactic anticoagulation treatment cannot reduce the incidence of thrombosis.On the contrary,it increases the incidence of non-serious bleeding.Therefore,prophylactic antico-agulation treatment is not recommended for outpatient COVID-19 patients.For COVID-19 hospitalized patients,when the base-line D-dimer level is≥2 times the upper limit,it is recommended to prioritize the use of therapeutic-dose anticoagulation;when the baseline D-dimer level is<2 times the upper limit,it is recommended to prioritize the use of intermediate/standard prophylactic-dose anticoagulation.
作者
李悦
何玉玲
常珊珊
LI Yue;HE Yuling;CHANG Shanshan(Department of Pharmacy,Tianjin First Central Hospital,Tianjin 300000,China;Department of Pharmacy,Tianjin Fourth Central Hospital,Tianjin 300140,China)
出处
《中国医院药学杂志》
北大核心
2025年第18期2142-2148,共7页
Chinese Journal of Hospital Pharmacy
