Spiro T E, Johnson G J, Christie M J, Lyons R M, MacFarlane D E, Blasier R B, Tremaine M D
Rhône-Poulenc Rorer Pharmaceuticals, Collegeville, Pennsylvania.
Ann Intern Med. 1994 Jul 15;121(2):81-9. doi: 10.7326/0003-4819-121-2-199407150-00001.
To determine the most effective and safe dose of enoxaparin to prevent deep venous thrombosis in high-risk surgical patients.
A double-blind, randomized, multicenter clinical trial.
Private, university, and government hospitals in the United States.
572 patients having elective hip replacement surgery, 568 of whom received study medication and had efficacy data available for evaluation.
Patients were randomly assigned to one of three subcutaneous enoxaparin regimens: 10 mg once daily (161 patients); 40 mg once daily (199 patients); and 30 mg every 12 hours (208 patients). Treatment was initiated within 24 hours after surgery and continued for as long as 7 days. Treatment with 10 mg enoxaparin once daily was discontinued prematurely after an interim analysis showed an increased deep venous thrombosis incidence in this treatment group.
Efficacy was determined by bilateral lower extremity venography, noninvasive vascular imaging methods, or clinical evidence on day 7 of treatment or earlier if clinically indicated.
Deep venous thrombosis occurred in 25% (40 of 161) of the patients who received 10 mg of enoxaparin once daily; in 14% (27 of 199) of those receiving 40 mg of enoxaparin once daily; and in 11% (22 of 208) in those receiving 30 mg of enoxaparin every 12 hours. The incidence of deep venous thrombosis was significantly higher in patients who received 10 mg of enoxaparin once daily compared with those who received 40 mg of enoxaparin once daily (P = 0.02) or those who received 30 mg of enoxaparin every 12 hours (P < 0.001). The difference between the patients who received 40 mg once daily and those who received 30 mg every 12 hours was not significant. Only two cases of pulmonary embolism were diagnosed, one in patients receiving 40 mg of enoxaparin and one in those receiving 10 mg once daily. The incidence of hemorrhagic complications differed significantly between patients who received 10 mg of enoxaparin once daily (5%, 8 of 161 patients) and those who received 30 mg of enoxaparin every 12 hours (13%, 26 of 208; P < 0.05).
After surgery, enoxaparin, 40 mg once daily or 30 mg every 12 hours, is more effective than a regimen of 10 mg once daily to prevent deep venous thrombosis in patients having elective hip replacement surgery. The regimens of 40 mg once daily and 30 mg every 12 hours provided prophylaxis similar to the most effective drug treatments previously reported. The incidence of hemorrhagic episodes with the regimens of 40 mg once daily and 30 mg twice daily was higher than that observed with 10 mg once daily; however, major hemorrhage occurred in only 4% to 5% of patients receiving the higher-dose regimens. The risk-to-benefit ratio supports the use of enoxaparin as a therapeutic agent to prevent deep venous thrombosis in these patients.
确定预防高危外科手术患者深静脉血栓形成的依诺肝素最有效且安全的剂量。
一项双盲、随机、多中心临床试验。
美国的私立、大学及政府医院。
572例行择期髋关节置换手术的患者，其中568例接受了研究用药并具有可供评估的疗效数据。
患者被随机分配至三种皮下注射依诺肝素方案之一：每日一次10毫克（161例患者）；每日一次40毫克（199例患者）；每12小时一次30毫克（208例患者）。术后24小时内开始治疗，持续长达7天。在一项中期分析显示该治疗组深静脉血栓形成发生率增加后，每日一次10毫克依诺肝素的治疗提前终止。
在治疗第7天或如有临床指征则更早，通过双侧下肢静脉造影、非侵入性血管成像方法或临床证据来确定疗效。
每日一次接受10毫克依诺肝素的患者中，25%（161例中的40例）发生深静脉血栓形成；每日一次接受40毫克依诺肝素的患者中这一比例为14%（199例中的27例）；每12小时接受30毫克依诺肝素的患者中为11%（208例中的22例）。每日一次接受10毫克依诺肝素的患者深静脉血栓形成发生率显著高于每日一次接受40毫克依诺肝素的患者（P = 0.02）或每12小时接受30毫克依诺肝素的患者（P < 0.001）。每日一次接受40毫克依诺肝素的患者与每12小时接受30毫克依诺肝素的患者之间差异不显著。仅诊断出2例肺栓塞，1例在接受40毫克依诺肝素的患者中，1例在每日一次接受10毫克的患者中。每日一次接受10毫克依诺肝素的患者（5%，161例中的8例）与每12小时接受30毫克依诺肝素的患者（13%，208例中的26例；P < 0.05）出血并发症发生率差异显著。
术后，每日一次40毫克或每12小时一次30毫克的依诺肝素方案在预防择期髋关节置换手术患者深静脉血栓形成方面比每日一次10毫克的方案更有效。每日一次40毫克和每12小时一次30毫克的方案提供的预防效果与先前报道的最有效的药物治疗相似。每日一次40毫克和每日两次30毫克方案的出血事件发生率高于每日一次10毫克方案；然而，接受高剂量方案的患者中仅4%至5%发生大出血。风险效益比支持使用依诺肝素作为预防这些患者深静脉血栓形成的治疗药物。
