Rivaroxaban for Thromboprophylaxis in High-Risk Ambulatory Patients with Cancer

• Khorana AA, Soff GA, Kakkar AK, et al. Rivaroxaban for Thromboprophylaxis in High-Risk Ambulatory Patients with Cancer. N Engl J Med 2019;380:720-8.
• Address reprint requests to Dr. Khorana at the Department of Hematology and Medical Oncology, Cleveland Clinic, 10201 Carnegie Ave., CA60, Cleveland, OH 44106, or at khorana@ ccf.org.

BACKGROUND 背景

Ambulatory patients receiving systemic cancer therapy are at varying risk for venous thromboembolism. However, the benefit of thromboprophylaxis in these patients is uncertain.

接受系統性癌症治療的非臥牀病人靜脈血栓栓塞的風險各不相同。然而，血栓預防在這些患者中的療效尚不確定。

METHODS 方法

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.

在這個雙盲隨機試驗中，納入高風險非臥牀癌症患者(Khorana評分≥2,該評分表範圍爲從0到6,得分越高表明靜脈血栓栓塞的風險更高),並且我們篩選沒有深靜脈血栓形成的患者並隨機分配每日接受rivaroxaban(10毫克的劑量)或安慰劑，共觀察180天,每8周篩查一次。

The primary efficacy end point was a composite of objectively confirmed proximal deep-vein thrombosis in a lower limb, pulmonary embolism, symptomatic deepvein 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.

主要療效終點爲客觀證實的下肢近端深靜脈血栓形成、肺栓塞、上肢有症狀的深靜脈血栓形成或下肢遠端深靜脈血栓形成以及靜脈血栓栓塞死亡，評估時間爲180天。一項涉及相同人羣的預先指定的支持性分析中，干預期間(從首次接受試驗藥物到持續劑量後加2天)使用相同的終點。主要的安全性終點事件是大出血。

RESULTS 結果

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.

在1080名入組患者中，49人(4.5%)在篩查時有血栓形成，沒有進行隨機分組。對於隨機分組的841名患者，在180天中，利伐沙班組420名患者中有25名(6.0%)出現了主要終點事件，安慰劑組421名患者中有37名(8.8%)出現了主要終點事件(危險比0.66;95%置信區間[CI]， 0.40 ~ 1.09;P = 0.10)。

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).

在預先指定的干預期分析中，利伐沙班組有11例(2.6%)患者出現了主要終點，安慰劑組有27例(6.4%)患者出現了主要終點事件(危險比0.40;95% CI, 0.20到0.80)；利伐沙班組405例患者中有8例(2.0%)出現大出血，安慰劑組404例(1.0%)中有4例(危險比1.96;95% CI, 0.59到6.49)。

CONCLUSION 結論

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.)

在180天的試驗期，對於高風險的癌症非臥牀患者，利伐沙班治療並沒有顯著降低靜脈血栓栓塞或靜脈血栓栓塞的死亡率。在干預期，利伐沙班大大降低了此類事件的發生率，大出血的發生率也較低。