VA Ann Arbor Healthcare System, 2215 Fuller Rd, Ann Arbor, MI, 48105, USA.
Drugs. 2019 Feb;79(3):291-302. doi: 10.1007/s40265-019-1059-y.
Acutely ill hospitalized medical patients remain at high thromboembolic risk for several weeks after discharge. Previous trials with extended-duration thromboprophylaxis using enoxaparin, apixaban, and rivaroxaban failed to achieve acceptable net clinical benefit, largely due to excess of major bleeding. Betrixaban is a novel factor Xa inhibitor with unique pharmacokinetic properties, including low renal clearance, long half-life, and low peak-to-trough ratio. The phase III APEX trial (N = 7513) compared a betrixaban 160 mg loading dose followed by 80 mg once daily for 35-42 days, with enoxaparin 40 mg once daily for 6-14 days; the betrixaban dose was reduced for renal impairment or a concomitant strong P-glycoprotein (P-gp) inhibitor. The primary efficacy endpoint of composite thrombotic events was not different between treatment arms in cohort 1 (D-dimer ≥ 2 × upper limit of normal). Subsequent exploratory analyses showed a statistically significant difference favoring betrixaban for symptomatic venous thromboembolism and net clinical benefit in the overall population. For the primary safety outcome, betrixaban did not significantly increase major bleeding compared with enoxaparin. Based on available data from the APEX trial and subanalyses, the use of betrixaban in patients similar to those enrolled in the APEX trial can reduce the risk of thromboembolic events without increasing the risk of major bleeding. Patients who may benefit more from betrixaban therapy include those with elevated D-dimer, history of venous thromboembolism, hospitalized for ischemic stroke, hospitalized for heart failure with N-terminal pro-B-type natriuretic peptide ≥ 1975 ng/L, or two or more VTE risk factors. Reduced-dose betrixaban does not appear to provide the same clinical utility as full-dose betrixaban.
急性病住院患者在出院后数周内仍存在高血栓栓塞风险。先前使用依诺肝素、阿哌沙班和利伐沙班进行延长疗程血栓预防的试验未能达到可接受的净临床获益，主要是由于大出血过多。贝曲西班是一种新型 Xa 因子抑制剂，具有独特的药代动力学特性，包括低肾清除率、长半衰期和低峰谷比。III 期 APEX 试验（N=7513）比较了贝曲西班 160mg 负荷剂量，随后每天 80mg 持续 35-42 天，与依诺肝素 40mg 每天一次持续 6-14 天；对于肾功能不全或同时使用强 P-糖蛋白（P-gp）抑制剂的患者，贝曲西班剂量减少。在队列 1（D-二聚体≥2×正常值上限）中，复合血栓事件的主要疗效终点在治疗组之间没有差异。随后的探索性分析显示，在总体人群中，贝曲西班在有症状静脉血栓栓塞和净临床获益方面具有统计学意义的优势。对于主要安全性结局，贝曲西班与依诺肝素相比，大出血没有显著增加。基于 APEX 试验和亚分析的现有数据，在类似于 APEX 试验入组患者中使用贝曲西班可以降低血栓栓塞事件的风险，而不会增加大出血的风险。可能从贝曲西班治疗中获益更多的患者包括 D-二聚体升高、静脉血栓栓塞史、因缺血性卒中住院、因 N 末端脑利钠肽前体≥1975ng/L 而住院的心衰患者，或有两个或更多 VTE 危险因素的患者。低剂量贝曲西班似乎不如全剂量贝曲西班提供相同的临床效果。
