ThrombosisResearch Unit, University of Calgary, Foothills Hospital, Calgary, Alberta, Canada.
Ann Intern Med. 2010 Jul 6;153(1):8-18. doi: 10.7326/0003-4819-153-1-201007060-00004.
Extended-duration low-molecular-weight heparin has been shown to prevent venous thromboembolism (VTE) in high-risk surgical patients.
To evaluate the efficacy and safety of extended-duration enoxaparin thromboprophylaxis in acutely ill medical patients.
Randomized, parallel, placebo-controlled trial. Randomization was computer-generated. Allocation was centralized. Patients, caregivers, and outcome assessors were blinded to group assignment. (ClinicalTrials.gov registration number: NCT00077753) SETTING: 370 sites in 20 countries across North and South America, Europe, and Asia.
Acutely ill medical patients 40 years or older with recently reduced mobility (bed rest or sedentary without [level 1] or with [level 2] bathroom privileges). Eligibility criteria for patients with level 2 immobility were amended to include only those who had additional VTE risk factors (age >75 years, history of VTE, or active or previous cancer) after interim analyses suggested lower-than-expected VTE rates.
Enoxaparin, 40 mg/d subcutaneously (2975 patients), or placebo (2988 patients), for 28 +/- 4 days after receiving open-label enoxaparin for an initial 10 +/- 4 days.
Incidence of VTE up to day 28 and of major bleeding events up to 48 hours after the last study treatment dose.
Extended-duration enoxaparin reduced VTE incidence compared with placebo (2.5% vs. 4%; absolute risk difference favoring enoxaparin, -1.53% [95.8% CI, -2.54% to -0.52%]). Enoxaparin increased major bleeding events (0.8% vs. 0.3%; absolute risk difference favoring placebo, 0.51% [95% CI, 0.12% to 0.89%]). The benefits of extended-duration enoxaparin seemed to be restricted to women, patients older than 75 years, and those with level 1 immobility.
Estimates of efficacy and safety for the overall trial population are difficult to interpret because of the change in eligibility criteria during the trial.
Use of extended-duration enoxaparin reduces VTE more than it increases major bleeding events in acutely ill medical patients with level 1 immobility, those older than 75 years, and women.
Sanofi-aventis.
延长疗程的低分子肝素已被证明可预防高危手术患者的静脉血栓栓塞症（VTE）。
评估急性病医学患者中延长疗程依诺肝素预防血栓的疗效和安全性。
随机、平行、安慰剂对照试验。随机由计算机生成。中央化分配。患者、护理人员和结果评估人员对分组分配不知情。（ClinicalTrials.gov 注册号：NCT00077753）
370 个地点分布在北美洲、南美洲、欧洲和亚洲的 20 个国家。
40 岁或以上的急性病医学患者，近期活动能力下降（卧床休息或久坐，无[1 级]或有[2 级]浴室便利设施）。2 级活动受限患者的纳入标准在中期分析后进行了修订，仅包括那些具有额外 VTE 风险因素（年龄>75 岁、VTE 病史或活动性或既往癌症）的患者，因为中期分析显示 VTE 发生率低于预期。
皮下注射依诺肝素 40mg/天（2975 例患者）或安慰剂（2988 例患者），在接受开放标签依诺肝素治疗 10±4 天初始疗程后 28±4 天。
直至第 28 天的 VTE 发生率和最后一次研究治疗剂量后 48 小时内的大出血事件发生率。
与安慰剂相比，延长疗程依诺肝素降低了 VTE 发生率（2.5%对 4%；依诺肝素组的绝对风险差异，-1.53%[95.8%CI，-2.54%至-0.52%]）。依诺肝素增加了大出血事件（0.8%对 0.3%；安慰剂组的绝对风险差异，0.51%[95%CI，0.12%至 0.89%]）。延长疗程依诺肝素的益处似乎仅限于女性、年龄>75 岁和 1 级活动受限的患者。
由于试验期间纳入标准的改变，对整个试验人群的疗效和安全性的估计难以解释。
在 1 级活动受限、年龄>75 岁和女性的急性病医学患者中，使用延长疗程的依诺肝素可降低 VTE 风险，同时增加大出血事件的风险。
赛诺菲-安万特。
