背景:有新兴的观察性研究(OS)来评估直接口服抗凝药(DOAC)在癌症相关血栓形成(CAT)中的实际有效性和安全性。我们进行了汇总和相互作用分析,以比较OS和随机对照试验(RCT)之间DOAC的治疗效果估计。
方法:我们系统地搜索了PUBMED,EMBASE和Cochrane库用于记录接受DOAC和常规抗凝药[华法林或低分子量肝素(LMWHs)]的CAT患者的复发性静脉血栓栓塞(VTE)和/或大出血事件的OSS和RCT。操作系统和随机对照试验的相对风险(RR)分别使用随机效应模型计算,随后应用相互作用分析来评估操作系统和随机对照试验之间的可比性。
结果:确定的10个操作系统(35,142例患者)和8个随机对照试验(2,602例患者)之间的基线特征相当。总的来说,未检测到OSs和RCTs之间的治疗效果估计值存在显著差异(复发性VTE的P交互作用:0.42;大出血的P交互作用:0.38).与常规抗凝剂相比,DOAC显著降低了CAT患者VTE复发的风险(RR:0.74,95%CI:0.63-0.86,I2:OSS为0%;RR:0.65,95%CI:0.49-0.86;I2:0%RCT),没有增加大出血风险(RR:0.90,95%CI:0.76-1.07,I2:24.0%,OSs;RR:1.17,95%CI:0.72-1.88,I2:26.2%,RCTs).然而,在CAT患者中,DOACs与常规抗凝剂相比,消化道出血(GIB)风险增加(RCTs的RR:2.77,95%CI:1.35~5.68,I2:0%).子群分析,根据比较器和随访持续时间,没有显着影响结果。
结论:在这项研究中,DOAC与常规抗凝剂在OS的CAT中的有效性和安全性与RCT的一致,证实在接受DOAC的CAT患者中,复发性VTE的风险较低,大出血的风险相似。
BACKGROUND: There are emerging observational studies (OSs) to assess real-world comparative effectiveness and safety of direct oral anticoagulants (DOACs) in cancer associated thrombosis (CAT). We conducted a pooled and interaction analysis to compare the treatment effect estimates of DOACs between OSs and randomized controlled trials (RCTs).
METHODS: We systematically searched PUBMED, EMBASE and Cochrane Library for OSs and RCTs that reported recurrent venous thromboembolism (VTE) and/or major bleeding events in CAT patients receiving DOACs and conventional anticoagulants [warfarin or low molecular-weight heparins (LMWHs)]. Relative risks (RRs) for OSs and RCTs were calculated using random-effects models separately, and interaction analyses were afterward applied to assess the comparability between OSs and RCTs.
RESULTS: Baseline characteristic was comparable between identified 10 OSs (35,142 patients) and 8 RCTs (2,602 patients). Overall, no significant difference of treatment effect estimates between OSs and RCTs was detected (Pinteraction: 0.42 for recurrent VTE; Pinteraction: 0.38 for major bleeding). DOACs significantly decreased the risk of recurrent VTE compared with conventional anticoagulants in CAT patients (RR: 0.74, 95% CI: 0.63-0.86, I2: 0% for OSs; RR: 0.65, 95% CI: 0.49-0.86; I2: 0% for RCTs), without increasing major bleeding risk (RR: 0.90, 95% CI: 0.76-1.07, I2: 24.0% for OSs; RR: 1.17, 95% CI: 0.72-1.88, I2: 26.2% for RCTs). Whereas, increased risk of gastrointestinal bleeding (GIB) was found with DOACs versus conventional anticoagulants in CAT patients (RR: 2.77, 95% CI: 1.35-5.68, I2: 0% for RCTs). Analyses of subgroups, based on comparators and follow-up duration, did not significantly affect results.
CONCLUSIONS: In this study, effectiveness and safety of DOACs versus conventional anticoagulants in CAT from OSs are in agreement with those from RCTs, confirming a low risk of recurrent VTE and similar risk of major bleeding in CAT patients receiving DOACs.