NEJM：口服直接Xa因子抑制剂治疗急性症状性肺栓塞患者

　　背景  研究已显示，固定剂量利伐沙班（一种口服Ⅹa 因子抑制剂）方案治疗深静脉血栓形成的疗效与标准抗凝疗法相同，且不需要实验室监测，这一方法也可能简化肺栓塞的治疗。

　　方法  在一项纳入4832 例患急性症状性肺栓塞、伴有或不伴有深静脉血栓形成患者的随机、开放标签、事件驱动的非劣效试验中，我们对利伐沙班（15 mg，2次/日，3周，随后为20 mg，1次/日）与依诺肝素继以调整剂量的维生素K拮抗剂治疗3、6 或12 周的标准治疗进行了比较。主要疗效转归为症状性复发性静脉血栓栓塞症。主要安全性转归为严重出血或临床相关的非严重出血。

　　结果  利伐沙班的主要有效性转归不劣于标准治疗（非劣效界值为2.0，P=0.003），利伐沙班组50 例次（2.1%）事件对标准治疗组44 例次（1.8%）事件[风险比为1.12，95%可信区间（CI）为0.75～1.68]。主要安全性转归发生于10.3%的利伐沙班组患者及11.4%的标准治疗组患者中（风险比为0.90，95%CI 为0.76～1.07，P=0.23）。在利伐沙班组的26 例患者（1.1%）及标准治疗组的52 例患者（2.2%）中，观察到了严重出血（风险比为0.49，95% CI 为0.31～0.79，P=0.003），两组其他不良事件发生率相似。

　　结论  固定剂量利伐沙班单药方案不劣于肺栓塞初始及长期治疗的标准疗法，并具有潜在的改善获益-风险特质。

Oral Rivaroxaban for the Treatment of Symptomatic Pulmonary Embolism

BACKGROUND

A fixed-dose regimen of rivaroxaban, an oral factor Xa inhibitor, has been shown to be as effective as standard anticoagulant therapy for the treatment of deep-vein thrombosis, without the need for laboratory monitoring. This approach may also simplify the treatment of pulmonary embolism.

METHODS

In a randomized, open-label, event-driven, noninferiority trial involving 4832 patients who had acute symptomatic pulmonary embolism with or without deep-vein thrombosis, we compared rivaroxaban (15 mg twice daily for 3 weeks, followed by 20 mg once daily) with standard therapy with enoxaparin followed by an adjusted-dose vitamin K antagonist for 3, 6, or 12 months. The primary efficacy outcome was symptomatic recurrent venous thromboembolism. The principal safety outcome was major or clinically relevant nonmajor bleeding.

RESULTS

Rivaroxaban was noninferior to standard therapy (noninferiority margin, 2.0; P=0.003) for the primary efficacy outcome, with 50 events in the rivaroxaban group (2.1%) versus 44 events in the standard-therapy group (1.8%) (hazard ratio, 1.12; 95% confidence interval [CI], 0.75 to 1.68). The principal safety outcome occurred in 10.3% of patients in the rivaroxaban group and 11.4% of those in the standard-therapy group (hazard ratio, 0.90; 95% CI, 0.76 to 1.07; P=0.23). Major bleeding was observed in 26 patients (1.1%) in the rivaroxaban group and 52 patients (2.2%) in the standard-therapy group (hazard ratio, 0.49; 95% CI, 0.31 to 0.79; P=0.003). Rates of other adverse events were similar in the two groups.

CONCLUSIONS

A fixed-dose regimen of rivaroxaban alone was noninferior to standard therapy for the initial and long-term treatment of pulmonary embolism and had a potentially improved benefit–risk profile. (Funded by Bayer HealthCare and Janssen Pharmaceuticals; EINSTEIN-PE ClinicalTrials.gov number, NCT00439777.)