Lassen Michael R, Dahl Ola, Mismetti Patrick, Zielske Dirk, Turpie Alexander G G
Hørsholm Hospital, Hørsholm, Denmark.
J Am Coll Cardiol. 2008 Apr 15;51(15):1498-504. doi: 10.1016/j.jacc.2008.03.007.
This study assessed the dose response of SR123781A for the prevention of venous thromboembolism (VTE) in patients undergoing total hip replacement (THR) surgery.
Despite VTE preventive measures, residual VTE complications still occur after THR. SR123781A, a synthetic oligosaccharide with a mixed profile of anti-factor Xa and IIa activities, could be an alternative to current treatments.
In this double-blind study, 1,023 patients undergoing THR were randomly assigned to 1 of 5 daily doses of SR123781A or to a calibrator arm of enoxaparin 40 mg. Treatment was continued for 10 days or until bilateral venography was performed after a minimum of 5 days.
A significant dose-response effect for VTE was observed for SR123781A (p < 0.0001). The VTE rates were 21.2%, 17.7%, 13.5%, 7.0%, and 4.4% in the 0.25-, 0.5-, 1.0-, 2.0-, and 4.0-mg dose groups of SR123781A, respectively, and 8.7% in the enoxaparin group. Doses of 2.0 and 4.0 mg of SR123781A reduced the risk of VTE by 67% and 79%, respectively, compared with the 0.25-mg dose group. Major bleeding was observed in 1.2%, 0.6%, 0.6%, 0.6%, and 5.8% of the patients in the 0.25-, 0.5-, 1.0-, 2.0-, and 4.0-mg dose groups of SR123781A, respectively, and in 0.6% of patients in the enoxaparin group. The dose-response effect for major bleeding was significant (p = 0.0037).
The model based on these dose-finding study results suggests that SR123781A doses ranging from 1.5 to 2.5 mg show a reasonable risk-to-benefit ratio for VTE prevention after major orthopedic surgery.
本研究评估了SR123781A预防全髋关节置换（THR）手术患者静脉血栓栓塞（VTE）的剂量反应。
尽管采取了VTE预防措施，但THR术后仍会出现残余VTE并发症。SR123781A是一种具有抗Xa因子和IIa因子活性混合特征的合成寡糖，可能是现有治疗方法的替代方案。
在这项双盲研究中，1023例接受THR手术的患者被随机分配至5种每日剂量的SR123781A中的1种或依诺肝素40mg校准组。治疗持续10天，或在至少5天后进行双侧静脉造影时停止。
观察到SR123781A对VTE有显著的剂量反应效应（p<0.0001）。SR123781A的0.25mg、0.5mg、1.0mg、2.0mg和4.0mg剂量组的VTE发生率分别为21.2%、17.7%、13.5%、7.0%和4.4%，依诺肝素组为8.7%。与0.25mg剂量组相比，2.0mg和4.0mg剂量的SR123781A分别将VTE风险降低了67%和79%。SR123781A的0.25mg、0.5mg、1.0mg、2.0mg和4.0mg剂量组的主要出血发生率分别为1.2%、0.6%、0.6%、0.6%和5.8%，依诺肝素组为0.6%。主要出血的剂量反应效应显著（p = 0.0037）。
基于这些剂量探索研究结果的模型表明，1.5至2.5mg的SR123781A剂量在预防重大骨科手术后的VTE方面显示出合理的风险效益比。
