Huisman Menno V, Klok Frederikus A
Department of Thrombosis and Hemostasis, Room C7-68g, Leiden University Medical Center, PO BOX 9600, 2300 RC Leiden, the Netherlands.
Eur Heart J Suppl. 2018 May;20(Suppl E):E12-E15. doi: 10.1093/eurheartj/suy016. Epub 2018 May 9.
Venous thromboembolism (VTE) in acute medically ill patients is a leading cause of in-hospital morbidity and mortality. A majority of these VTE events occur post-discharge, and patients remain at increased VTE risk for up to 3 months post-discharge. Recent clinical trials of extended-duration thromboprophylaxis with enoxaparin, rivaroxaban, and apixaban in acute medically ill patients did not demonstrate a net clinical benefit compared with in-hospital thromboprophylaxis, and were shown to be associated with higher risks of major bleeding. Betrixaban is a new direct oral anticoagulant (DOAC) with a different pharmacokinetic profile than other DOACs. Betrixaban has the longest half-life among the DOAC class, with a terminal half-life of 35-45 h and an effective half-life of 19-27 h. Betrixaban has a low peak-to-trough ratio compared with other anticoagulants and a predictable duration of drug exposure, leading to overall consistent anticoagulant effect over 24 h. Betrixaban is mainly cleared via the hepatobiliary system and therefore not contraindicated in patients with severe renal insufficiency. Betrixaban was recently approved for the indication of extended thromboprophylaxis in the United States based on the APEX trial of betrixaban 80 mg once daily for 35-42 days compared with low molecular weight heparin enoxaparin for 10 ± 4 days in hospitalized acute medically ill patients. This study demonstrated that extended-duration betrixaban reduced VTE compared with standard-duration enoxaparin in acute medically ill patients, without increased risk of major bleeding. This patient population at risk of VTE may benefit from extended prophylaxis, ensuring continuum of care from in-hospital to post-discharge.
急性内科疾病患者的静脉血栓栓塞症（VTE）是住院患者发病和死亡的主要原因。这些VTE事件大多发生在出院后，患者在出院后长达3个月内VTE风险持续增加。近期针对急性内科疾病患者使用依诺肝素、利伐沙班和阿哌沙班进行延长疗程血栓预防的临床试验表明，与住院期间血栓预防相比，并未显示出净临床获益，且显示出更高的大出血风险。贝曲西班是一种新型直接口服抗凝剂（DOAC），其药代动力学特征与其他DOAC不同。在DOAC类别中，贝曲西班的半衰期最长，终末半衰期为35 - 45小时，有效半衰期为19 - 27小时。与其他抗凝剂相比，贝曲西班的峰谷比低，药物暴露持续时间可预测，从而在24小时内产生总体一致的抗凝效果。贝曲西班主要通过肝胆系统清除，因此在严重肾功能不全患者中并非禁忌。基于APEX试验，贝曲西班最近在美国被批准用于延长血栓预防的适应证，该试验将住院急性内科疾病患者中每日一次服用80 mg贝曲西班35 - 42天与服用10±4天的低分子肝素依诺肝素进行比较。这项研究表明，与标准疗程的依诺肝素相比，延长疗程的贝曲西班在急性内科疾病患者中可降低VTE，且不增加大出血风险。这类有VTE风险的患者可能从延长预防中获益，确保从住院到出院后的连续护理。
