NOAC与VKA口服抗凝药在预防和治疗活动性癌症患者血栓性疾病中有效性和安全性的荟萃分析

Efficacy and safety of non-vitamin K antagonist versus vitamin K antagonist oral anticoagulants in the prevention and treatment of thrombotic disease in active cancer patients:a systematic review and meta-analysis of randomized controlled trials

目的比较非维生素K拮抗剂口服抗凝药(NOAC)与传统维生素K拮抗剂(VKA)在活动性癌症患者中预防和治疗血栓性疾病的有效性和安全性。方法在PubMed、Web of Science和Clinical Trials数据库中检索2019年5月前关于活动性癌症患者使用NOAC与VKA的随机对照试验(RCT)或原始研究设计为RCT的二次研究,语种限制为中、英文。由2名研究者依据筛选策略独立进行文献筛选与资料提取,评价文献质量,评估跨研究间数据汇总分析的适宜性,并检测主要结局事件异质性。比较NOAC与VKA在活动性癌症合并静脉血栓栓塞(VTE),或合并非瓣膜性心房颤动(NVAF)患者中,发生大出血、非大出血性临床相关出血、VTE、卒中和全因死亡的相对风险(RR)和95%置信区间(CI)。结果共纳入9篇文献,4篇为原始研究,5篇为二次研究。其中活动性癌症伴VTE 5篇(5/9),伴NVAF 4篇(4/9)。共包含4049例(68.86%)例活动性癌症患者,其中2278例(56.26%)接受NOAC治疗,1771例(43.74%)接受VKA治疗。纳入文献质量均较高(得分均≥5分),各纳入文献数据可进行汇总分析(P>0.05),结局事件异质性低(I2均<25%)。在活动性癌症伴VTE患者中,服用NOAC患者VTE复发(RR=0.55,95%CI:0.36~0.84,P=0.005)和非大出血性临床相关出血事件(RR=0.77,95%CI:0.60~0.98,P=0.03)风险低于VKA。在活动性癌症伴NVAF患者中,与VKA比较,NOAC在预防VTE和卒中、减少非大出血性临床相关出血事件、大出血及全因死亡上差异无统计学意义(P>0.05)。结论对于伴有VTE或NVAF的活动性癌症患者,在预防和治疗血栓性疾病时,相对于VKA,NOAC在疗效与安全性方面更具优势。

Object We aimed to compare the efficacy and safety of non-vitamin K antagonist oral anticoagulants(NOAC)and vitamin K antagonist(VKA)in the prevention and treatment of thrombotic diseases in patients with active cancer.Methods To find randomized controlled trials(RCT)in which NOACs were compared VKAs in active cancer,we searched the electronic databases(PubMed,Web of Science and Clinical Trials)up to May 2019 and and languages restricted to Chinese and English.According to the screening strategy,two researchers independently screened and extracted literature,evaluated the quality of literature,the suitability of collected cross study data for analysis,and tested the heterogeneity.The relative risk(RR)and 95%confidence interval(95%CI)of major bleeding,clinically related non-major bleeding,VTE,stroke and all-cause mortality in active cancer patients with VTE,active cancer patients with non-valvular atrial fibrillation(NVAF)was calculated and the results were compared between NOAC with VKA.Results A total of 9 RCTs were included,including 5 cancers with VTE(5/9)and 4 cancers with NVAF(4/9).A total of 5867 patients were included.After excluding 1818(30.99%)patients with cancer history,4049(68.86%)patients with active cancer were statistically analyzed.Among them,2278(56.26%)received NOAC treatment,1771 patients(43.74%)received VKA treatment.The quality of the included documents was high(all scores were>5 points),and the data of each included document could be summarized and analyzed(P>0.05).The heterogeneity of main outcome events was very low(I2=0).In VTE patients with active cancer,NOACs were more effective in reducing recurrence of VTE(RR=0.55,95%CI 0.36-0.84;P=0.005)and clinically related non-major bleeding(RR=0.77,95%CI 0.60-0.98;P=0.03)than VKAs.In NVAF patients with active cancer,efficacy of NOACs and VKAs was similar in terms of reducing VTE,stroke,clinically related non-major bleeding,major bleeding and all-cause mortality events(P>0.05).Conclusions For patients with active cancer accompanied by VTE,NOAC may has more advantages in efficacy and safety compared to VKA in the prevention and treatment of thrombotic diseases.