Yamashita Yugo, Morimoto Takeshi, Muraoka Nao, Shioyama Wataru, Chatani Ryuki, Shibata Tatsuhiro, Nishimoto Yuji, Ogihara Yoshito, Doi Kosuke, Oi Maki, Shiga Taro, Sueta Daisuke, Kim Kitae, Tanabe Yasuhiro, Koitabashi Norimichi, Takada Takuma, Ikeda Satoshi, Nakagawa Hitoshi, Tsukahara Kengo, Shoji Masaaki, Sakamoto Jiro, Hisatake Shinji, Ogino Yutaka, Fujita Masashi, Nakanishi Naohiko, Dohke Tomohiro, Hiramori Seiichi, Nawada Ryuzo, Kaneda Kazuhisa, Ono Koh, Kimura Takeshi
Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University, Japan (Y.Y., K.O.).
Department of Clinical Epidemiology, Hyogo Medical University, Nishinomiya, Japan (T.M.).
Circulation. 2025 Mar 4;151(9):589-600. doi: 10.1161/CIRCULATIONAHA.124.072758. Epub 2024 Nov 18.
The optimal duration of anticoagulation therapy for patients with cancer and acute low-risk pulmonary embolism (PE) is clinically relevant, but evidence is lacking. Prolonged anticoagulation therapy could have a potential benefit for prevention of thrombotic events; however, it could also increase the risk of bleeding.
In a multicenter, open-label, adjudicator-blinded, randomized clinical trial at 32 institutions in Japan, we randomly assigned patients with cancer and acute low-risk PE of the simplified version of the Pulmonary Embolism Severity Index score of 1, in a 1:1 ratio, to receive either an 18-month or a 6-month rivaroxaban treatment. The primary end point was recurrent venous thromboembolism (VTE) at 18 months. The major secondary end point was major bleeding at 18 months according to the criteria of the International Society on Thrombosis and Hemostasis. The primary hypothesis was that an 18-month treatment was superior to a 6-month treatment in terms of the primary end point.
From February 2021 to March 2023, 179 patients were randomized, and after the exclusion of one patient who withdrew consent, 178 were included in the intention-to-treat population: 89 patients in the 18-month rivaroxaban group and 89 in the 6-month rivaroxaban group. The mean age was 65.7 years; 47% of the patients were men, and 12% had symptoms of PE at baseline. The primary end point of recurrent VTE occurred in 5 of the 89 patients (5.6%) in the 18-month rivaroxaban group and in 17 of the 89 (19.1%) in the 6-month rivaroxaban group (odds ratio, 0.25 [95% CI, 0.09-0.72]; =0.01). Among 22 recurrent VTE, 5 patients presented with a symptomatic recurrent VTE; recurrent PE occurred in 11 patients, including 2 with main and 4 with lobar PEs; and recurrent deep vein thrombosis was seen in 11 patients, including 3 with proximal deep vein thromboses. The major secondary end point of major bleeding occurred in 7 of the 89 patients (7.8%) in the 18-month rivaroxaban group and in 5 of the 89 patients (5.6%) in the 6-month rivaroxaban group (odds ratio, 1.43 [95% CI, 0.44-4.70]; =0.55).
In patients with cancer and acute low-risk PE of the simplified version of the Pulmonary Embolism Severity Index score of 1, the 18-month rivaroxaban treatment was superior to the 6-month rivaroxaban treatment with respect to recurrent VTE events.
URL: https://www.clinicaltrials.gov; Unique identifier: NCT04724460.
癌症合并急性低风险肺栓塞（PE）患者的最佳抗凝治疗时长具有临床相关性，但相关证据不足。延长抗凝治疗可能对预防血栓形成事件有潜在益处；然而，这也可能增加出血风险。
在日本32家机构进行的一项多中心、开放标签、评判者盲法、随机临床试验中，我们将简化版肺栓塞严重程度指数评分为1的癌症合并急性低风险PE患者按1:1比例随机分配，分别接受18个月或6个月的利伐沙班治疗。主要终点为18个月时复发性静脉血栓栓塞（VTE）。主要次要终点为根据国际血栓与止血学会标准在18个月时发生的大出血。主要假设是在主要终点方面，18个月治疗优于6个月治疗。
从2021年2月至2023年3月，179例患者被随机分组，在排除1例撤回同意的患者后，178例被纳入意向性治疗人群：18个月利伐沙班组89例患者，6个月利伐沙班组89例患者。平均年龄为65.7岁；47%的患者为男性，12%的患者基线时有PE症状。18个月利伐沙班组89例患者中有5例（5.6%）发生复发性VTE这一主要终点事件，6个月利伐沙班组89例患者中有17例（19.1%）发生（优势比，0.25 [95% CI，0.09 - 0.72]；P = 0.01）。在22例复发性VTE中，5例患者出现有症状的复发性VTE；11例患者发生复发性PE，其中2例为主要PE，4例为肺叶PE；11例患者发生复发性深静脉血栓形成，其中3例为近端深静脉血栓形成。大出血这一主要次要终点事件在18个月利伐沙班组89例患者中有7例（7.8%）发生，6个月利伐沙班组89例患者中有5例（5.6%）发生（优势比，1.43 [95% CI，0.44 - 4.70]；P = 0.55）。
对于简化版肺栓塞严重程度指数评分为1的癌症合并急性低风险PE患者，在复发性VTE事件方面，18个月利伐沙班治疗优于6个月利伐沙班治疗。
