Division of Cardiovascular Medicine, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Boston Clinical Research Institute, Newton, MA, USA.
Intensive Care Med. 2019 Apr;45(4):477-487. doi: 10.1007/s00134-019-05565-6. Epub 2019 Feb 18.
To assess the efficacy and safety of betrixaban for venous thromboembolism (VTE) prophylaxis among critically ill patients.
The APEX trial randomized 7513 acutely ill hospitalized patients to betrixaban for 35-42 days or enoxaparin for 10 ± 4 days. Among those, 703 critically ill patients admitted to the intensive care unit were included in the analysis, and 547 patients who had no severe renal insufficiency or P-glycoprotein inhibitor use were included in the full-dose stratum. The risk of VTE, bleeding, net clinical benefit (composite of VTE and major bleeding), and mortality was compared at 35-42 days and at 77 days.
At 35-42 days, extended betrixaban reduced the risk of VTE (4.27% vs 7.95%, P = 0.042) without causing excess major bleeding (1.14% vs 3.13%, P = 0.07). Both VTE (3.32% vs 8.33%, P = 0.013) and major bleeding (0.00% vs 3.26%, P = 0.003) were decreased in the full-dose stratum. Patients who received betrixaban had more non-major bleeding than enoxaparin (overall population: 2.56% vs 0.28%, P = 0.011; full-dose stratum: 3.32% vs 0.36%, P = 0.010). Mortality was similar at the end of study (overall population: 13.39% vs 16.19%, P = 0.30; full-dose stratum: 13.65% vs 16.30%, P = 0.39).
Compared with shorter-duration enoxaparin, critically ill medical patients who received extended-duration betrixaban had fewer VTE without more major bleeding events. The benefit of betrixaban was driven by preventing asymptomatic thrombosis and offset by an elevated risk of non-major bleeding. The APEX trial did not stratify by intensive care unit admission and the present study included a highly selected population of critically ill patients. These hypothesis-generating findings need to be validated in future studies.
http://www.clinicaltrials.gov . Unique identifier: NCT01583218.
评估贝曲西班用于预防重症患者静脉血栓栓塞症（VTE）的疗效和安全性。
APE 试验将 7513 名急性住院患者随机分为贝曲西班组（35-42 天）或依诺肝素组（10±4 天）。其中，703 名重症患者被收入重症监护病房进行分析，547 名无严重肾功能不全或 P-糖蛋白抑制剂使用者被纳入全剂量亚组。在 35-42 天和 77 天比较 VTE、出血、净临床获益（VTE 和主要出血的复合终点）和死亡率。
在 35-42 天，延长贝曲西班治疗降低了 VTE 风险（4.27% vs 7.95%，P=0.042），但未增加大出血（1.14% vs 3.13%，P=0.07）。全剂量亚组中 VTE（3.32% vs 8.33%，P=0.013）和主要出血（0.00% vs 3.26%，P=0.003）均降低。贝曲西班组非主要出血发生率高于依诺肝素组（总体人群：2.56% vs 0.28%，P=0.011；全剂量亚组：3.32% vs 0.36%，P=0.010）。研究结束时死亡率相似（总体人群：13.39% vs 16.19%，P=0.30；全剂量亚组：13.65% vs 16.30%，P=0.39）。
与较短疗程的依诺肝素相比，接受延长疗程贝曲西班的重症内科患者 VTE 发生率较低，且无更多大出血事件。贝曲西班的获益来自于预防无症状血栓形成，而非主要出血风险的增加则相抵。APE 试验未按重症监护病房入院分层，本研究纳入了高度选择的重症患者人群。这些生成假说的发现需要在未来的研究中验证。
