Edoxaban for the Treatment of Cancer-Associated Venous Thromboembolism

被引：1203

作者：

Raskob, Gary E. ^{[1
]}

van Es, Nick ^{[2
]}

Verhamme, Peter ^{[4
]}

Carrier, Marc ^{[5
]}

Di Nisio, Marcello ^{[10
]}

Garcia, David ^{[11
]}

Grosso, Michael A. ^{[12
]}

Kakkar, Ajay K. ^{[13
,14
]}

Kovacs, Michael J. ^{[6
]}

Mercuri, Michele F. ^{[12
]}

Meyer, Guy ^{[15
]}

Segers, Annelise ^{[3
]}

Shi, Minggao ^{[12
]}

Wang, Tzu-Fei ^{[16
]}

Yeo, Erik ^{[7
]}

Zhang, George ^{[12
]}

Zwicker, Jeffrey I. ^{[17
]}

Weitz, Jeffrey I. ^{[8
,9
]}

Buller, Harry R. ^{[2
]}

机构：

[1] Univ Oklahoma, Hlth Sci Ctr, Coll Publ Hlth, 801 NE 13th St, Oklahoma City, OK 73104 USA

[2] Univ Amsterdam, Acad Med Ctr, Dept Vasc Med, Amsterdam, Netherlands

[3] Acad Res Org, ITREAS, Amsterdam, Netherlands

[4] Univ Hosp Leuven, Dept Vasc Med & Hemostasis, Leuven, Belgium

[5] Ottawa Hosp Res Inst, Ottawa, ON, Canada

[6] Victoria Hosp, London Hlth Sci Ctr, London, ON, Canada

[7] Univ Toronto, Univ Hlth Network, Toronto, ON, Canada

[8] McMaster Univ, Hamilton, ON, Canada

[9] Thrombosis & Atherosclerosis Res Inst, Hamilton, ON, Canada

[10] Univ G DAnnunzio, Dept Med & Aging Sci, Chieti, Italy

[11] Univ Washington, Dept Med, Div Hematol, Seattle, WA 98195 USA

[12] Daiichi Sankyo Pharma Dev, Basking Ridge, NJ USA

[13] Thrombosis Res Inst, London, England

[14] UCL, London, England

[15] Hop Europeen Georges Pompidou, AP HP, Dept Resp Dis, Paris, France

[16] Ohio State Univ, Wexner Med Ctr, Columbus, OH 43210 USA

[17] Beth Israel Deaconess Med Ctr, Harvard Med Sch, Boston, MA 02215 USA

来源：

NEW ENGLAND JOURNAL OF MEDICINE | 2018年 / 378卷 / 07期

关键词：

VITAMIN-K ANTAGONISTS; TREATMENT GUIDELINES; PROPHYLAXIS; MANAGEMENT; THROMBOSIS;

D O I：

10.1056/NEJMoa1711948

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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.)

引用

页码：615 / 624

页数：10

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