Breddin H K, Hach-Wunderle V, Nakov R, Kakkar V V
International Institute of Thrombosis and Vascular Diseases, Frankfurt, Germany.
N Engl J Med. 2001 Mar 1;344(9):626-31. doi: 10.1056/NEJM200103013440902.
Low-molecular-weight heparins are frequently used to treat venous thromboembolism, but optimal dosing regimens and clinical outcomes need further definition.
In this multicenter, open-label study with blinded adjudication of end points, we randomly assigned patients with acute deep-vein thrombosis to one of three treatment regimens: intravenous administration of unfractionated heparin; subcutaneous administration of a low-molecular-weight heparin, reviparin, twice a day for one week; or subcutaneous administration of reviparin once a day for four weeks. The primary end point was evidence of regression of the thrombus on venography on day 21; secondary end points were recurrent venous thromboembolism, major bleeding within 90 days after enrollment, and death.
Of the patients receiving unfractionated heparin, 40.2 percent (129 of 321) had thrombus regression, as compared with 53.4 percent (175 of 328) of patients receiving reviparin twice daily and 53.5 percent (167 of 312) of the patients receiving reviparin once daily. With regard to thrombus regression, reviparin administered twice daily was significantly more effective than unfractionated heparin (relative likelihood of thrombus regression, 1.28; 97.5 percent confidence interval, 1.08 to 1.52), as was reviparin administered once daily (relative likelihood, 1.29; 97.5 percent confidence interval, 1.08 to 1.53). Mortality and the frequency of episodes of major bleeding were similar in the three groups.
In acute deep-vein thrombosis, reviparin regimens are more effective than unfractionated heparin in reducing the size of the thrombus. Reviparin is also more effective than unfractionated heparin for the prevention of recurrent thromboembolism and equally safe.
低分子量肝素常用于治疗静脉血栓栓塞症，但最佳给药方案和临床疗效仍需进一步明确。
在这项多中心、开放标签且终点采用盲法判定的研究中，我们将急性深静脉血栓形成患者随机分配至三种治疗方案之一：静脉注射普通肝素；皮下注射低分子量肝素瑞肝素，每日两次，共一周；或皮下注射瑞肝素，每日一次，共四周。主要终点是第21天静脉造影显示血栓消退的证据；次要终点是复发性静脉血栓栓塞、入组后90天内的大出血和死亡。
接受普通肝素治疗的患者中，40.2%（321例中的129例）血栓消退，而每日两次接受瑞肝素治疗的患者中这一比例为53.4%（328例中的175例），每日一次接受瑞肝素治疗的患者中这一比例为53.5%（312例中的167例）。在血栓消退方面，每日两次注射瑞肝素比普通肝素显著更有效（血栓消退的相对可能性为1.28；97.5%置信区间为1.08至1.52），每日一次注射瑞肝素也是如此（相对可能性为1.29；97.5%置信区间为1.08至1.53）。三组的死亡率和大出血发生率相似。
在急性深静脉血栓形成中，瑞肝素方案在减小血栓大小方面比普通肝素更有效。瑞肝素在预防复发性血栓栓塞方面也比普通肝素更有效，且安全性相当。
