Fujisaki Tomohiro, Sueta Daisuke, Yamamoto Eiichiro, Buckley Conor, Sacchi de Camargo Correia Guilherme, Aronson Julia, Tallón de Lara Paulino, Fujisue Koichiro, Usuku Hiroki, Matsushita Kenichi, Mehran Roxana, Dangas George D, Tsujita Kenichi
Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center, Osaka, Japan.
JACC CardioOncol. 2024 Jan 9;6(1):99-113. doi: 10.1016/j.jaccao.2023.10.009. eCollection 2024 Feb.
Current guidelines recommend several direct oral anticoagulant agents (DOACs) equally for managing cancer-associated venous thromboembolism (VTE).
The aim of this study was to assess the efficacy and safety of DOACs in patients with active cancer.
Literature searches were conducted in PubMed, Embase, and Cochrane Central in November 2022. Randomized controlled trials investigating anticoagulation strategies (vitamin K antagonists, parenteral anticoagulation [eg, low-molecular weight heparin], and DOACs) for VTE in patients with active cancer were identified for network meta-analysis. The outcomes included recurrent VTE, recurrent pulmonary embolism, recurrent deep venous thrombosis, major bleeding, clinically relevant nonmajor bleeding (CRNMB), and a composite outcome of major bleeding or CRNMB. Pooled HRs and 95% CIs were estimated using either the HR or relative risk provided from each study. Random-effects models were used for all the analyses.
Seventeen randomized controlled trials involving 6,623 patients with active cancer were included. No significant differences were found among the DOACs for efficacy outcomes (recurrent VTE, pulmonary embolism, and deep venous thrombosis). In terms of major bleeding, apixaban was similarly safe compared with dabigatran and rivaroxaban but was associated with a decreased risk compared with edoxaban (HR: 0.38; 95% CI: 0.15-0.93). Regarding CRNMB, edoxaban was similarly safe compared with apixaban but was associated with a decreased risk compared with rivaroxaban (HR: 0.31; 95% CI: 0.10-0.91). Compared with parenteral anticoagulation, apixaban was associated with a reduced risk for recurrent VTE (HR: 0.60; 95% CI: 0.38-0.93) without increasing bleeding, edoxaban was associated with an increased risk for major bleeding or CRNMB (HR: 1.35; 95% CI: 1.02-1.79), and rivaroxaban was associated with an increased risk for CRNMB (HR: 3.76; 95% CI: 1.43-9.88).
DOACs demonstrate comparable efficacy but exhibit different safety profiles. Apixaban may confer an antithrombotic benefit without an increased risk for bleeding, distinguishing it from other contemporary anticoagulation strategies in patients with active cancer and VTE.
当前指南推荐几种直接口服抗凝剂(DOACs)在治疗癌症相关静脉血栓栓塞症(VTE)方面疗效相当。
本研究旨在评估DOACs在活动性癌症患者中的疗效和安全性。
2022年11月在PubMed、Embase和Cochrane Central进行文献检索。纳入针对活动性癌症患者VTE的抗凝策略(维生素K拮抗剂、胃肠外抗凝剂[如低分子肝素]和DOACs)的随机对照试验,进行网状Meta分析。结局指标包括复发性VTE、复发性肺栓塞、复发性深静脉血栓形成、大出血、临床相关非大出血(CRNMB)以及大出血或CRNMB的复合结局。使用各研究提供的HR或相对风险估计合并HR和95%CI。所有分析均采用随机效应模型。
纳入17项涉及6623例活动性癌症患者的随机对照试验。DOACs在疗效结局(复发性VTE、肺栓塞和深静脉血栓形成)方面未发现显著差异。在大出血方面,阿哌沙班与达比加群和利伐沙班相比安全性相似,但与依度沙班相比风险降低(HR:0.38;95%CI:0.15 - 0.93)。关于CRNMB,依度沙班与阿哌沙班相比安全性相似,但与利伐沙班相比风险降低(HR:0.31;95%CI:0.10 - 0.91)。与胃肠外抗凝剂相比,阿哌沙班复发性VTE风险降低(HR:0.60;95%CI:0.38 - 0.93)且不增加出血风险,依度沙班大出血或CRNMB风险增加(HR:1.35;95%CI:1.02 - 1.79),利伐沙班CRNMB风险增加(HR:3.76;95%CI:1.43 - 9.88)。
DOACs显示出相当的疗效,但具有不同的安全性特征。阿哌沙班可能在不增加出血风险的情况下带来抗血栓益处,这使其在活动性癌症和VTE患者中区别于其他当代抗凝策略。