Gibson C Michael, Jennings Lisa K, Chi Gerald, Yee Megan K, Halaby Rim, Nafee Tarek, AlKhalfan Fahad, Kerneis Mathieu, Korjian Serge, Daaboul Yazan, Goldhaber Samuel Z, Hull Russel D, Hernandez Adrian F, Cohen Alexander T, Harrington Robert A
Cardiovascular Division, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, United States.
CirQuest Labs, The University of Tennessee Health Science Center, Memphis, Tennessee, United States.
TH Open. 2018 Jan 8;2(1):e16-e24. doi: 10.1055/s-0037-1615288. eCollection 2018 Jan.
Elevated D-dimer concentrations are associated with an increased risk of venous thromboembolism (VTE). However, they may also provide prognostic value. The present analysis sought to study the association of D-dimer levels with VTE event rates and the efficacy of betrixaban versus enoxaparin in the APEX trial. Hospitalized acutely medically ill subjects ( = 7,513) were randomized in a double-dummy double-blind fashion to either extended-duration oral betrixaban (80 mg once daily for 35-42 days) or standard dose subcutaneous enoxaparin (40 mg once daily for 10 ± 4 days) for venous thromboprophylaxis. D-dimer was assessed using a central core laboratory measurement. For every 0.25 µg/mL increase in D-dimer concentration, there was a 2% increase in the relative risk of experiencing the primary efficacy endpoint (asymptomatic deep vein thrombosis [DVT], symptomatic DVT, nonfatal pulmonary embolism, or VTE-related death) in both the betrixaban ( < 0.001) and enoxaparin ( < 0.001) treatment arms. Among D-dimer-positive (≥ 2 × upper limit of normal; corresponding to ≥ 1.00 µg/mL) subjects, extended-duration betrixaban reduced the risk of experiencing the primary efficacy outcome (5.4% [ = 124] vs. 7.6% [ = 170]; odds ratio = 0.69; 95% confidence interval: 0.55-0.88; absolute risk reduction = 2.2%, number needed to treat = 46, = 0.003). There was no interaction between D-dimer and the treatment effect ( = 0.53). Extended-duration betrixaban was superior to standard-duration enoxaparin, irrespective of D-dimer level at baseline. To prevent one VTE event, 46 D-dimer-positive patients would need to be treated with betrixaban.
D - 二聚体浓度升高与静脉血栓栓塞症（VTE）风险增加相关。然而，它们也可能具有预后价值。本分析旨在研究APEX试验中D - 二聚体水平与VTE事件发生率的关联以及贝曲西班与依诺肝素的疗效对比。 急性内科疾病住院患者（n = 7513）以双模拟双盲方式随机分为接受延长疗程口服贝曲西班（80mg每日一次，共35 - 42天）或标准剂量皮下注射依诺肝素（40mg每日一次，共10±4天）进行静脉血栓预防。D - 二聚体采用中央核心实验室检测方法进行评估。 在贝曲西班（P < 0.001）和依诺肝素（P < 0.001）治疗组中，D - 二聚体浓度每增加0.25μg/mL，发生主要疗效终点（无症状深静脉血栓形成[DVT]、有症状DVT、非致命性肺栓塞或VTE相关死亡）的相对风险增加2%。在D - 二聚体阳性（≥2×正常上限；相当于≥1.00μg/mL）的受试者中，延长疗程的贝曲西班降低了发生主要疗效结局的风险（5.4%[n = 124]对7.6%[n = 170]；比值比 = 0.69；95%置信区间：0.55 - 0.88；绝对风险降低 = 2.2%，需治疗人数 = 46，P = 0.003）。D - 二聚体与治疗效果之间无交互作用（P = 0.53）。 无论基线D - 二聚体水平如何，延长疗程的贝曲西班均优于标准疗程的依诺肝素。为预防1例VTE事件，需要对46例D - 二聚体阳性患者使用贝曲西班进行治疗。
