Eriksson Bengt I, Dahl Ola E, Rosencher Nadia, Kurth Andreas A, van Dijk C Niek, Frostick Simon P, Prins Martin H, Hettiarachchi Rohan, Hantel Stefan, Schnee Janet, Büller Harry R
Department of Orthopaedic Surgery, Sahlgrenska University Hospital/Ostra, Gothenburg, Sweden.
Lancet. 2007 Sep 15;370(9591):949-56. doi: 10.1016/S0140-6736(07)61445-7.
After hip replacement surgery, prophylaxis following discharge from hospital is recommended to reduce the risk of venous thromboembolism. Our aim was to assess the oral, direct thrombin inhibitor dabigatran etexilate for such prophylaxis.
In this double-blind study, we randomised 3494 patients undergoing total hip replacement to treatment for 28-35 days with dabigatran etexilate 220 mg (n=1157) or 150 mg (1174) once daily, starting with a half-dose 1-4 h after surgery, or subcutaneous enoxaparin 40 mg once daily (1162), starting the evening before surgery. The primary efficacy outcome was the composite of total venous thromboembolism (venographic or symptomatic) and death from all causes during treatment. On the basis of the absolute difference in rates of venous thromboembolism with enoxaparin versus placebo, the non-inferiority margin for the difference in rates of thromboembolism was defined as 7.7%. Efficacy analyses were done by modified intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00168818.
Median treatment duration was 33 days. 880 patients in the dabigatran etexilate 220 mg group, 874 in the dabigatran etexilate 150 mg group, and 897 in the enoxaparin group were available for the primary efficacy outcome analysis; the main reasons for exclusion in all three groups were the lack of adequate venographic data. The primary efficacy outcome occurred in 60 (6.7%) of 897 individuals in the enoxaparin group versus 53 (6.0%) of 880 patients in the dabigatran etexilate 220 mg group (absolute difference -0.7%, 95% CI -2.9 to 1.6%) and 75 (8.6%) of 874 people in the 150 mg group (1.9%, -0.6 to 4.4%). Both doses were thus non-inferior to enoxaparin. There was no significant difference in major bleeding rates with either dose of dabigatran etexilate compared with enoxaparin (p=0.44 for 220 mg, p=0.60 for 150 mg). The frequency of increases in liver enzyme concentrations and of acute coronary events during the study did not differ significantly between the groups.
Oral dabigatran etexilate was as effective as enoxaparin in reducing the risk of venous thromboembolism after total hip replacement surgery, with a similar safety profile.
髋关节置换术后，建议出院后进行预防以降低静脉血栓栓塞风险。我们的目的是评估口服直接凝血酶抑制剂达比加群酯用于此类预防的效果。
在这项双盲研究中，我们将3494例行全髋关节置换术的患者随机分为三组，分别接受达比加群酯220mg（n = 1157）或150mg（n = 1174）每日一次治疗28 - 35天，术后1 - 4小时开始给予半量起始剂量，或皮下注射依诺肝素40mg每日一次（n = 1162），术前一晚开始给药。主要疗效结局为治疗期间总的静脉血栓栓塞（静脉造影或有症状）和全因死亡的复合终点。根据依诺肝素与安慰剂相比静脉血栓栓塞发生率的绝对差异，将血栓栓塞发生率差异的非劣效界值定义为7.7%。疗效分析采用改良意向性分析。本试验已在ClinicalTrials.gov注册，注册号为NCT00168818。
中位治疗持续时间为33天。达比加群酯220mg组880例、达比加群酯150mg组874例和依诺肝素组897例患者可用于主要疗效结局分析；三组排除的主要原因均为缺乏充分的静脉造影数据。依诺肝素组897例患者中有60例（6.7%）发生主要疗效结局，达比加群酯220mg组880例患者中有53例（6.0%）发生（绝对差异 - 0.7%，95%CI - 2.9%至1.6%），150mg组874例患者中有75例（8.6%）发生（1.9%， - 0.6%至4.4%）。因此，两种剂量的达比加群酯均不劣于依诺肝素。与依诺肝素相比，两种剂量的达比加群酯主要出血率均无显著差异（220mg组p = 0.44，150mg组p = 0.60）。研究期间，各组肝酶浓度升高和急性冠脉事件的发生频率无显著差异。
口服达比加群酯在降低全髋关节置换术后静脉血栓栓塞风险方面与依诺肝素同样有效，且安全性相似。
