van Hylckama Vlieg Marte A M, Nasserinejad Kazem, Visser Chantal, Bramer Wichor M, Ashrani Aneel A, Bosson Jean-Luc, Crusan Daniel J, D'Alessio Andrea, Fluharty Meg E, Ģībietis Valdis, Hansson Per-Olof, Hara Nobuhiro, Jara-Palomares Luis, Kraaijpoel Noémie, Mahé Isabelle, Marshall Andrea, Ogino Yutaka, Otero Remedios, Versmissen Jorie, Klok Frederikus A, Kruip Marieke J H A, van der Rijt Carin C D, Geijteman Eric C T
Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, the Netherlands.
Department of Haematology, Erasmus MC, University Medical Center, Rotterdam, the Netherlands.
EClinicalMedicine. 2023 Sep 8;64:102194. doi: 10.1016/j.eclinm.2023.102194. eCollection 2023 Oct.
The optimal duration of anticoagulation in patients with active cancer and venous thromboembolism (VTE) is unknown. Current clinical guidelines advocate anticoagulant therapy for 3-6 months and to continue anticoagulant therapy for as long as the cancer is active. However, an adequate systematic review on the rate of recurrent VTE after discontinuation of anticoagulant therapy has not been performed.
For this systemic review and meta-analysis, we searched Embase.com, Medline (Ovid), Web of Science, Cochrane Library, and Google Scholar, from database inception to February 16, 2023, for studies on anticoagulant therapy in patients with cancer and the recurrence of venous thromboembolism after discontinuation of this therapy. We included randomised controlled trials and cohort studies published in English that reported on patients who met the following: cancer and a first VTE, completed at least 3 months of anticoagulant therapy, were followed after discontinuation of anticoagulant therapy, and with symptomatic recurrent VTE as an outcome during follow-up. Study-level data were requested from study authors. The primary outcome was the rate of recurrent VTE after discontinuation of anticoagulant therapy. A Bayesian random-effects meta-analysis was used to estimate the rate of recurrent VTE per 100 person-years for the pooled studies at different time intervals after discontinuation of anticoagulation therapy. We also calculated the cumulative VTE recurrence rate at different time intervals. Forest plots were mapped and the results were summarized by the median and 95% credible interval (CIs). This study was registered with PROSPERO, CRD42021249060.
Of 3856 studies identified in our search, 33 studies were identified for inclusion. After requesting study-level data, 14 studies involving 1922 patients with cancer-associated thrombosis were included. The pooled rate of recurrent VTE per 100 person-years after discontinuation of anticoagulant therapy was 14.6 events (95% credible interval 6.5-22.8) in the first three months, decreasing to 1.1 events (95% CI 0.3-2.1) in year 2-3, and 2.2 events (95% CI 0.0-4.4) in year 3-5 after discontinuation of anticoagulant therapy. The cumulative VTE recurrence rate was 28.3% (95% CI 15.6-39.6%) at 1 year; 31.1% (95% CI 16.5-43.8%) at 2 years; 31.9% (95% CI 16.8-45.0%) at 3 years; and 35.0% (95% CI 16.8-47.4%) at 5 years after discontinuation of anticoagulant therapy.
This meta-analysis demonstrates a high rate of recurrent VTE over time after discontinuation of anticoagulant therapy in patients with cancer-associated thrombosis. Our results support the current clinical guidelines to continue anticoagulant therapy in patients with active cancer.
Erasmus MC.
活动性癌症合并静脉血栓栓塞（VTE）患者的最佳抗凝持续时间尚不清楚。当前临床指南提倡进行3 - 6个月的抗凝治疗，并在癌症处于活动期时持续进行抗凝治疗。然而，尚未对抗凝治疗中断后VTE复发率进行充分的系统评价。
对于这项系统评价和荟萃分析，我们检索了Embase.com、Medline（Ovid）、Web of Science、Cochrane图书馆和谷歌学术，检索时间从数据库建立至2023年2月16日，以查找关于癌症患者抗凝治疗以及该治疗中断后静脉血栓栓塞复发情况的研究。我们纳入了以英文发表的随机对照试验和队列研究，这些研究报告的患者符合以下条件：患有癌症且首次发生VTE、完成了至少3个月的抗凝治疗、在抗凝治疗中断后进行随访，并且在随访期间以有症状的复发性VTE作为结局。向研究作者索取研究水平的数据。主要结局是抗凝治疗中断后VTE复发率。采用贝叶斯随机效应荟萃分析来估计抗凝治疗中断后不同时间间隔汇总研究中每100人年的VTE复发率。我们还计算了不同时间间隔的累积VTE复发率。绘制森林图，结果以中位数和95%可信区间（CI）进行总结。本研究已在国际前瞻性系统评价注册库（PROSPERO）注册，注册号为CRD42021249060。
在我们检索到的3856项研究中，有33项研究被确定纳入。在索取研究水平的数据后，纳入了14项涉及1922例癌症相关血栓形成患者的研究。抗凝治疗中断后，前三个月每100人年的VTE复发汇总率为14.6例（95%可信区间6.5 - 22.8），在中断治疗后的第2 - 3年降至1.1例（95% CI 0.3 - 2.1），第3 - 5年为2.2例（95% CI 0.0 - 4.4）。抗凝治疗中断后1年的累积VTE复发率为28.3%（95% CI 15.6 - 39.6%）；2年时为31.1%（95% CI 16.5 - 43.8%）；3年时为31.9%（95% CI 16.8 - 45.0%）；5年时为35.0%（95% CI 16.8 - 47.4%）。
这项荟萃分析表明，癌症相关血栓形成患者抗凝治疗中断后，随着时间推移VTE复发率较高。我们的结果支持当前临床指南中对活动性癌症患者继续进行抗凝治疗的建议。
伊拉斯谟医学中心。
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