Lee Agnes Y Y, Levine Mark N, Baker Ross I, Bowden Chris, Kakkar Ajay K, Prins Martin, Rickles Frederick R, Julian Jim A, Haley Susan, Kovacs Michael J, Gent Michael
Department of Medicine, McMaster University, Hamilton, Ont., Canada.
N Engl J Med. 2003 Jul 10;349(2):146-53. doi: 10.1056/NEJMoa025313.
Patients with cancer have a substantial risk of recurrent thrombosis despite the use of oral anticoagulant therapy. We compared the efficacy of a low-molecular-weight heparin with that of an oral anticoagulant agent in preventing recurrent thrombosis in patients with cancer.
Patients with cancer who had acute, symptomatic proximal deep-vein thrombosis, pulmonary embolism, or both were randomly assigned to receive low-molecular-weight heparin (dalteparin) at a dose of 200 IU per kilogram of body weight subcutaneously once daily for five to seven days and a coumarin derivative for six months (target international normalized ratio, 2.5) or dalteparin alone for six months (200 IU per kilogram once daily for one month, followed by a daily dose of approximately 150 IU per kilogram for five months).
During the six-month study period, 27 of 336 patients in the dalteparin group had recurrent venous thromboembolism, as compared with 53 of 336 patients in the oral-anticoagulant group (hazard ratio, 0.48; P=0.002). The probability of recurrent thromboembolism at six months was 17 percent in the oral-anticoagulant group and 9 percent in the dalteparin group. No significant difference between the dalteparin group and the oral-anticoagulant group was detected in the rate of major bleeding (6 percent and 4 percent, respectively) or any bleeding (14 percent and 19 percent, respectively). The mortality rate at six months was 39 percent in the dalteparin group and 41 percent in the oral-anticoagulant group.
In patients with cancer and acute venous thromboembolism, dalteparin was more effective than an oral anticoagulant in reducing the risk of recurrent thromboembolism without increasing the risk of bleeding.
尽管使用了口服抗凝治疗，但癌症患者仍有较高的复发性血栓形成风险。我们比较了低分子量肝素与口服抗凝剂在预防癌症患者复发性血栓形成方面的疗效。
患有急性、有症状的近端深静脉血栓形成、肺栓塞或两者皆有的癌症患者被随机分配接受低分子量肝素（达肝素），剂量为每公斤体重200 IU，皮下注射，每日一次，共五至七天，随后接受香豆素衍生物治疗六个月（目标国际标准化比值为2.5），或仅接受达肝素治疗六个月（每公斤体重200 IU，每日一次，共一个月，随后五个月每日剂量约为每公斤体重150 IU）。
在为期六个月的研究期间，达肝素组336例患者中有27例发生复发性静脉血栓栓塞，而口服抗凝剂组336例患者中有53例发生（风险比为0.48；P = 0.002）。口服抗凝剂组六个月时复发性血栓栓塞的概率为17%，达肝素组为9%。达肝素组和口服抗凝剂组在大出血发生率（分别为6%和4%）或任何出血发生率（分别为14%和19%）方面未检测到显著差异。达肝素组六个月时的死亡率为39%，口服抗凝剂组为41%。
在患有癌症和急性静脉血栓栓塞的患者中，达肝素在降低复发性血栓栓塞风险方面比口服抗凝剂更有效，且不增加出血风险。
