Gibson C Michael, Korjian Serge, Chi Gerald, Daaboul Yazan, Jain Purva, Arbetter Douglas, Goldhaber Samuel Z, Hull Russel, Hernandez Adrian F, Lopes Renato D, Gold Alex, Cohen Alexander T, Harrington Robert A
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.
J Am Heart Assoc. 2017 Jul 11;6(7):e006015. doi: 10.1161/JAHA.117.006015.
Extended-duration betrixaban showed a significant reduction in venous thromboembolism in the APEX trial (Acute Medically Ill VTE Prevention With Extended Duration Betrixaban Study). Given the variable clinical impact of different efficacy and safety events, one approach to assess net clinical outcomes is to include only those events that are either fatal or cause irreversible harm.
This was a post hoc analysis of the APEX trial-a multicenter, double-blind, randomized controlled trial comparing extended-duration betrixaban versus standard-of-care enoxaparin. A composite of all fatal or irreversible safety (fatal bleeding or intracranial hemorrhage) and efficacy events (cardiopulmonary death, myocardial infarction, pulmonary embolism, and ischemic stroke) was evaluated in a time-to-first event analysis. In patients with positive D-dimer results, betrixaban reduced fatal or irreversible events at 35 to 42 days (4.80% versus 3.54%; hazard ratio, 0.73; absolute risk reduction, 1.26%; number needed to treat, 79 [=0.033]) and at study end at 77 days (6.27% versus 4.36%; hazard ratio, 0.70; absolute risk reduction, 1.91%; number needed to treat, 52 [=0.005]) versus enoxaparin. In all patients, betrixaban reduced fatal or irreversible events at 35 to 42 days (4.08% versus 2.90%; hazard ratio, 0.71; absolute risk reduction, 1.18%; number needed to treat, 86 [=0.006]) and 77 days (5.17% versus 3.64%; hazard ratio, 0.70; absolute risk reduction, 1.53%; number needed to treat, 65 [=0.002]).
Among hospitalized medically ill patients, extended-duration betrixaban demonstrated an ≈30% reduction in fatal or irreversible ischemic or bleeding events compared with standard-duration enoxaparin. A total of 65 patients would require treatment with betrixaban to prevent 1 fatal or irreversible event versus enoxaparin.
URL: http://www.ClinicalTrials.gov. Unique identifier: NCT01583218.
在APEX试验（急性内科疾病患者延长疗程使用贝曲西班预防静脉血栓栓塞症研究）中，延长疗程的贝曲西班显著降低了静脉血栓栓塞症的发生率。鉴于不同疗效和安全性事件对临床的影响各异，一种评估净临床结局的方法是仅纳入那些致命或导致不可逆损害的事件。
这是对APEX试验的一项事后分析，该试验是一项多中心、双盲、随机对照试验，比较了延长疗程的贝曲西班与标准治疗药物依诺肝素。在首次事件发生时间分析中，评估了所有致命或不可逆安全性事件（致命性出血或颅内出血）和疗效事件（心肺死亡、心肌梗死、肺栓塞和缺血性卒中）的复合事件。在D-二聚体结果为阳性的患者中，与依诺肝素相比，贝曲西班在35至42天（4.80%对3.54%；风险比，0.73；绝对风险降低，1.26%；需治疗人数，79 [=0.033]）和研究结束时77天（6.27%对4.36%；风险比，0.70；绝对风险降低，1.91%；需治疗人数，52 [=0.005]）时降低了致命或不可逆事件的发生率。在所有患者中，贝曲西班在35至42天（4.08%对2.90%；风险比，0.71；绝对风险降低，1.18%；需治疗人数，86 [=0.006]）和77天（5.17%对3.64%；风险比，0.70；绝对风险降低，1.53%；需治疗人数，65 [=0.002]）时降低了致命或不可逆事件的发生率。
在住院内科疾病患者中，与标准疗程的依诺肝素相比，延长疗程的贝曲西班使致命或不可逆缺血或出血事件减少了约30%。与依诺肝素相比，总共需要65例患者接受贝曲西班治疗才能预防1例致命或不可逆事件。
