Samaranayake Chinthaka B, Anderson James, McCabe Colm, Zahir Syeda Farah, W Upham John, Keir Gregory
Faculty of Medicine, University of Queensland, Brisbane, Queensland, Australia.
Department of Respiratory and Sleep Medicine, Princess Alexandra Hospital, Brisbane, Queensland, Australia.
Intern Med J. 2022 Feb;52(2):272-281. doi: 10.1111/imj.15049.
Several recent randomised controlled trials (RCT) have investigated the use of direct oral anticoagulants (DOAC) in the treatment of malignancy-associated venous thromboembolism (VTE).
This meta-analysis combines all RCT data to determine the risks of recurrent VTE and bleeding with DOAC in patients with malignancy-associated VTE compared with low-molecular-weight heparin (LMWH).
The study followed PRISMA guidelines. MEDLINE, EMBASE and CENTRAL were systematically searched from inception to 1 April 2020. References of reviews and relevant conference proceedings were searched by hand. Two authors independently evaluated study eligibility, extracted data and assessed risk of bias. Direct and indirect meta-analyses were performed.
In four RCT with low risk of bias (2907 patients), high certainty evidence suggested that DOAC had a 37% reduction in risk of recurrent VTE compared with LMWH (direct pooled risk ratio (RR) 0.63; 95% confidence interval (CI) 0.44-0.91; I = 28%). No significant difference was observed in the risk of major bleeding with DOAC compared with LMWH (RR 1.31; 95% CI 0.83-2.07; I = 22%; moderate certainty evidence), including in patients in gastrointestinal and genitourinary malignancy. An increased risk of combined major or clinically relevant non-major bleeding was seen with DOAC (RR 1.52; 95% CI 1.09-2.12; I = 51%; low certainty evidence). Apixaban had the highest probability of being ranked the most effective and least bleeding risk among the DOAC.
DOAC are effective in treating malignancy associated VTE; however, caution is required in patients with high risk of bleeding. Apixaban had lower risk of bleeding compared to other DOAC in this population.
近期多项随机对照试验(RCT)研究了直接口服抗凝剂(DOAC)在治疗恶性肿瘤相关静脉血栓栓塞症(VTE)中的应用。
本荟萃分析整合了所有RCT数据,以确定与低分子肝素(LMWH)相比,DOAC治疗恶性肿瘤相关VTE患者时复发性VTE和出血的风险。
本研究遵循PRISMA指南。从数据库建立至2020年4月1日,系统检索了MEDLINE、EMBASE和CENTRAL数据库。通过手工检索综述的参考文献和相关会议记录。两位作者独立评估研究的纳入资格、提取数据并评估偏倚风险。进行了直接和间接荟萃分析。
在四项偏倚风险较低的RCT(共2907例患者)中,高确定性证据表明,与LMWH相比,DOAC使复发性VTE风险降低37%(直接合并风险比(RR)0.63;95%置信区间(CI)0.44 - 0.91;I = 28%)。与LMWH相比,DOAC在大出血风险方面未观察到显著差异(RR 1.31;95% CI 0.83 - 2.07;I = 22%;中等确定性证据),包括胃肠道和泌尿生殖系统恶性肿瘤患者。DOAC使大出血或临床相关非大出血合并风险增加(RR 1.52;95% CI 1.09 - 2.12;I = 51%;低确定性证据)。在DOAC中,阿哌沙班被评为最有效且出血风险最低的可能性最高。
DOAC在治疗恶性肿瘤相关VTE方面有效;然而,出血风险高的患者需谨慎使用。在该人群中,与其他DOAC相比,阿哌沙班出血风险较低。