Edoxaban for the Treatment of Cancer-Associated Venous Thromboembolism
Edoxaban for the Treatment of Cancer-Associated Venous Thromboembolism
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DOI：
10.1056/nejmoa1711948
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发表时间：
2018-02-15
影响因子：
158.5
通讯作者：
Buller, Harry R.
中科院分区：
文献类型：
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作者：
Raskob, Gary E.;van Es, Nick;Buller, Harry R.
低分子肝素是癌症相关静脉血栓栓塞的标准治疗。直接口服抗凝剂治疗的作用尚不清楚。我们将有急性症状或偶发性静脉血栓栓塞的癌症患者随机分为两组，一组接受低分子量肝素治疗至少5天，另一组口服依度沙班，剂量为60 mg，每日一次。（依度沙班组）或皮下注射达肝素，剂量为200 IU/kg体重，每日一次，持续1个月，然后是达肝素，剂量为150 IU/kg，每日一次（达肝素组）。治疗至少6个月，最长12个月。主要结果是在随机分组后的12个月内复发静脉血栓栓塞或大出血的复合物，无论治疗持续时间如何，在1050例接受随机分组的患者中，1046例被纳入改良的意向治疗分析。依度沙班组522例患者中有67例（12.8%）发生主要结局事件，而达肝素组524例患者中有71例（13.5%）发生主要结局事件（风险比，0.97; 95%置信区间[CI]，0.70 - 1.36;非劣效性P = 0.006;优效性P = 0.87）。依度沙班组41例患者（7.9%）和达肝素组59例患者（11.3%）发生复发性静脉血栓栓塞（风险差异，-3.4个百分点; 95% CI，-7.0至0.2）。依度沙班组36例（6.9%）和达肝素组21例（4.0%）患者发生大出血（风险差异为2.9个百分点; 95%CI为0.1 ~ 5.6）。结论：就复发性静脉血栓栓塞或大出血的复合结局而言，口服依度沙班不劣于皮下注射达肝素。依度沙班组静脉血栓栓塞复发率较低，但大出血发生率高于达肝素组。（由Daiichi Sankyo资助; Hokusai VTE癌症临床试验。政府编号，NCT 02073682。）
BACKGROUND Low-molecular-weight heparin is the standard treatment for cancer-associated venous thromboembolism. The role of treatment with direct oral anticoagulant agents is unclear.METHODS In this open-label, noninferiority trial, we randomly assigned patients with cancer who had acute symptomatic or incidental venous thromboembolism to receive either low-molecular-weight heparin for at least 5 days followed by oral edoxaban at a dose of 60 mg once daily (edoxaban group) or subcutaneous dalteparin at a dose of 200 IU per kilogram of body weight once daily for 1 month followed by dalteparin at a dose of 150 IU per kilogram once daily (dalteparin group). Treatment was given for at least 6 months and up to 12 months. The primary outcome was a composite of recurrent venous thromboembolism or major bleeding during the 12 months after randomization, regardless of treatment duration.RESULTS Of the 1050 patients who underwent randomization, 1046 were included in the modified intention-to-treat analysis. A primary-outcome event occurred in 67 of the 522 patients (12.8%) in the edoxaban group as compared with 71 of the 524 patients (13.5%) in the dalteparin group (hazard ratio, 0.97; 95% confidence interval [CI], 0.70 to 1.36; P = 0.006 for noninferiority; P = 0.87 for superiority). Recurrent venous thromboembolism occurred in 41 patients (7.9%) in the edoxaban group and in 59 patients (11.3%) in the dalteparin group (difference in risk, -3.4 percentage points; 95% CI, -7.0 to 0.2). Major bleeding occurred in 36 patients (6.9%) in the edoxaban group and in 21 patients (4.0%) in the dalteparin group (difference in risk, 2.9 percentage points; 95% CI, 0.1 to 5.6).CONCLUSIONS Oral edoxaban was noninferior to subcutaneous dalteparin with respect to the composite outcome of recurrent venous thromboembolism or major bleeding. The rate of recurrent venous thromboembolism was lower but the rate of major bleeding was higher with edoxaban than with dalteparin. (Funded by Daiichi Sankyo; Hokusai VTE Cancer ClinicalTrials. gov number, NCT02073682.)