Gibson C Michael, Halaby Rim, Korjian Serge, Daaboul Yazan, Arbetter Douglas F, Yee Megan K, Goldhaber Samuel Z, Hull Russel, Hernandez Adrian F, Lu Shiao-Ping, Bandman Olga, Leeds Janet M, Gold Alex, Harrington Robert A, Cohen Alexander T
Cardiovascular Division, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA.
Cardiovascular Division, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA.
Am Heart J. 2017 Mar;185:93-100. doi: 10.1016/j.ahj.2016.12.004. Epub 2016 Dec 18.
The APEX trial assessed the safety and efficacy of extended-duration thromboprophylaxis using betrixaban versus standard dosing of enoxaparin among hospitalized, acutely ill medical patients. The 80-mg betrixaban dose was halved to 40 mg among subjects with severe renal insufficiency and those receiving a concomitant strong P-glycoprotein inhibitor.
This analysis assessed the pharmacokinetics, efficacy, and safety of full- (80 mg) and reduced-dose (40 mg) betrixaban relative to enoxaparin in the APEX trial.
The median concentration of betrixaban among subjects administered the 80-mg dose was higher than that of the 40-mg dose (19 ng/mL vs 11 ng/mL, P<.001). In the primary analysis cohort 1 (d-dimer ≥2× upper limit of normal), the primary efficacy outcome (asymptomatic proximal deep vein thrombosis, symptomatic proximal or distal deep vein thrombosis, symptomatic nonfatal pulmonary embolism, or venous thromboembolism-related death) was significantly reduced among subjects treated with 80 mg of extended-duration betrixaban versus enoxaparin (6.27% [95/1516] vs 8.39% [130/1549], relative risk reduction=0.26 [0.04-0.42], P=.023), and similarly in the entire primary efficacy outcome population (4.87% [122/2506] vs 7.06% [181/2562], relative risk reduction=0.30 [0.13-0.44], P=.001). There was no difference in the primary outcome for subjects treated with 40 mg betrixaban vs enoxaparin across cohorts. In addition, there was no excess of major bleeding associated with either betrixaban dose compared with enoxaparin.
The 80-mg betrixaban dose achieves higher plasma concentrations than the 40-mg dose and, in contrast to the 40-mg dose, is associated with improved efficacy across all cohorts relative to standard-dose enoxaparin without an excess risk of major bleeding in the management of medically ill subjects.
APEX试验评估了在住院急性病内科患者中，使用贝曲西班进行延长疗程的血栓预防与依诺肝素标准剂量相比的安全性和有效性。在严重肾功能不全患者以及接受强效P-糖蛋白抑制剂的患者中，贝曲西班80毫克的剂量减半至40毫克。
该分析在APEX试验中评估了全剂量（80毫克）和减量（40毫克）贝曲西班相对于依诺肝素的药代动力学、有效性和安全性。
接受80毫克剂量的受试者中贝曲西班的中位浓度高于40毫克剂量的受试者（19纳克/毫升对11纳克/毫升，P<0.001）。在主要分析队列1（D-二聚体≥正常上限的2倍）中，与依诺肝素相比，接受80毫克延长疗程贝曲西班治疗的受试者的主要疗效结局（无症状近端深静脉血栓形成、有症状的近端或远端深静脉血栓形成、有症状的非致命性肺栓塞或静脉血栓栓塞相关死亡）显著降低（6.27%[95/1516]对8.39%[130/1549]，相对风险降低=0.26[0.04-0.42]，P=0.023），在整个主要疗效结局人群中情况类似（4.87%[122/2506]对7.06%[181/2562]，相对风险降低=0.30[0.13-0.44]，P=0.001）。在各队列中，接受40毫克贝曲西班治疗的受试者与接受依诺肝素治疗的受试者在主要结局方面没有差异。此外，与依诺肝素相比，两种贝曲西班剂量均未出现更多的大出血情况。
80毫克贝曲西班剂量比40毫克剂量能达到更高的血浆浓度，并且与40毫克剂量不同，相对于标准剂量的依诺肝素，在所有队列中其疗效均有改善，在治疗内科疾病患者时不会增加大出血风险。
