利伐沙班预防高风险门诊癌症患者血栓栓塞症。
Rivaroxaban for Thromboprophylaxis in High-Risk Ambulatory Patients with Cancer.
机构信息
From the Department of Hematology and Medical Oncology, Taussig Cancer Institute and Case Comprehensive Cancer Center, Cleveland Clinic, Cleveland (A.A.K.); the Department of Medicine, Memorial Sloan Kettering Cancer Center (G.A.S., E.M.O.), and Weill Cornell Medical College (G.A.S., E.M.O.), New York; the Thrombosis Research Institute and University College London, London (A.K.K.); University of Texas M.D. Anderson Cancer Center, Houston (S.V.-R.), and U.S. Oncology Research-Texas Oncology, Tyler (H.A.Y.) - both in Texas; the Department of Medicine, Charité Universitätsmedizin Berlin, Berlin (H.R.); the Division of Hematology-Oncology, University of California Davis School of Medicine, Sacramento (T.W.), and the Keck School of Medicine, University of Southern California, Los Angeles (H.A.L.); the Division of Hematology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore (M.B.S.); the University of Washington School of Medicine (D.A.G., N.M.K., G.H.L.), Advanced Cancer Research Group (N.M.K.), and Fred Hutchinson Cancer Research Center (G.H.L.), Seattle; Penn State Cancer Institute, Milton S. Hershey Medical Center, Hershey, PA (C.P.B.); the Department of Cancer Pharmacology, Levine Cancer Institute, Atrium Health, Charlotte, NC (J.N.P.); Janssen Scientific Affairs, Titusville (P.W., P.B., S.K.), and Janssen Research and Development, Raritan (U.V.) - both in New Jersey; the Department of Medicine, McMaster University, Hamilton, ON, Canada (J.E.); the Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN (R.M.); and the Division of Hematology-Oncology, Beth Israel Deaconess Medical Center, Boston (K.A.B.).
出版信息
N Engl J Med. 2019 Feb 21;380(8):720-728. doi: 10.1056/NEJMoa1814630.
BACKGROUND
Ambulatory patients receiving systemic cancer therapy are at varying risk for venous thromboembolism. However, the benefit of thromboprophylaxis in these patients is uncertain.
METHODS
In this double-blind, randomized trial involving high-risk ambulatory patients with cancer (Khorana score of ≥2, on a scale from 0 to 6, with higher scores indicating a higher risk of venous thromboembolism), we randomly assigned patients without deep-vein thrombosis at screening to receive rivaroxaban (at a dose of 10 mg) or placebo daily for up to 180 days, with screening every 8 weeks. The primary efficacy end point was a composite of objectively confirmed proximal deep-vein thrombosis in a lower limb, pulmonary embolism, symptomatic deep-vein thrombosis in an upper limb or distal deep-vein thrombosis in a lower limb, and death from venous thromboembolism and was assessed up to day 180. In a prespecified supportive analysis involving the same population, the same end point was assessed during the intervention period (first receipt of trial agent to last dose plus 2 days). The primary safety end point was major bleeding.
RESULTS
Of 1080 enrolled patients, 49 (4.5%) had thrombosis at screening and did not undergo randomization. Of the 841 patients who underwent randomization, the primary end point occurred in 25 of 420 patients (6.0%) in the rivaroxaban group and in 37 of 421 (8.8%) in the placebo group (hazard ratio, 0.66; 95% confidence interval [CI], 0.40 to 1.09; P = 0.10) in the period up to day 180. In the prespecified intervention-period analysis, the primary end point occurred in 11 patients (2.6%) in the rivaroxaban group and in 27 (6.4%) in the placebo group (hazard ratio, 0.40; 95% CI, 0.20 to 0.80). Major bleeding occurred in 8 of 405 patients (2.0%) in the rivaroxaban group and in 4 of 404 (1.0%) in the placebo group (hazard ratio, 1.96; 95% CI, 0.59 to 6.49).
CONCLUSIONS
In high-risk ambulatory patients with cancer, treatment with rivaroxaban did not result in a significantly lower incidence of venous thromboembolism or death due to venous thromboembolism in the 180-day trial period. During the intervention period, rivaroxaban led to a substantially lower incidence of such events, with a low incidence of major bleeding. (Funded by Janssen and others; CASSINI ClinicalTrials.gov number, NCT02555878.).
背景
接受全身癌症治疗的门诊患者存在不同程度的静脉血栓栓塞风险。然而，这些患者使用血栓预防治疗的获益并不明确。
方法
在这项涉及高风险门诊癌症患者（Khorana 评分≥2，评分范围为 0 至 6，评分越高表示静脉血栓栓塞风险越高）的双盲、随机试验中，我们将未在筛查时发生深静脉血栓的患者随机分为接受利伐沙班（剂量为 10mg）或安慰剂治疗组，每日用药，持续 180 天，每 8 周筛查一次。主要疗效终点为下肢深静脉近端血栓形成、肺栓塞、上肢症状性深静脉血栓形成或下肢远端深静脉血栓形成以及静脉血栓栓塞导致的死亡的复合终点，评估时间截至 180 天。在一项针对相同人群的预先指定的支持性分析中，该终点在干预期间（首次接受试验药物至最后一剂加 2 天）进行评估。主要安全性终点为大出血。
结果
在 1080 名入组患者中，49 名（4.5%）在筛查时发生血栓，未进行随机分组。在 841 名接受随机分组的患者中，在 180 天的时间内，利伐沙班组有 25 名（6.0%）患者和安慰剂组有 37 名（8.8%）患者发生主要终点事件（风险比，0.66；95%置信区间[CI]，0.40 至 1.09；P=0.10）。在预先指定的干预期分析中，利伐沙班组有 11 名（2.6%）患者和安慰剂组有 27 名（6.4%）患者发生主要终点事件（风险比，0.40；95%CI，0.20 至 0.80）。利伐沙班组有 8 名（2.0%）患者和安慰剂组有 4 名（1.0%）患者发生大出血（风险比，1.96；95%CI，0.59 至 6.49）。
结论
在高风险的门诊癌症患者中，与安慰剂相比，利伐沙班治疗并未在 180 天的试验期间显著降低静脉血栓栓塞或静脉血栓栓塞导致的死亡发生率。在干预期间，利伐沙班显著降低了此类事件的发生率，且大出血发生率较低。（由 Janssen 等资助；CASSINI 临床试验.gov 编号，NCT02555878。）
Zotero 插件