van Den Belt A G, Prins M H, Lensing A W, Castro A A, Clark O A, Atallah A N, Burihan E
Academic Medical Center, Clinical Epidemiology & Biostatistics, J. 2-221, PO Box 22700, 1100 DE Amsterdam, Netherlands.
Cochrane Database Syst Rev. 2000(2):CD001100. doi: 10.1002/14651858.CD001100.
Low molecular weight heparins have been shown to be effective and safe for prevention of venous thromboembolism. There is accumulating evidence that these new anticoagulants are also effective and safe for treatment of venous thromboembolism.
The objective of this review was to determine the effect of fixed-dose, subcutaneous low molecular weight heparins compared with adjusted-dose, intravenous or subcutaneous, unfractionated heparin for initial treatment of acute deep venous thrombosis or pulmonary embolism.
Trials were identified from the Cochrane Peripheral Vascular Diseases Group trials register and LILACS. The reviewers contacted colleagues and representatives of pharmaceutical companies for additional information about trials.
Randomised trials comparing fixed-dose, subcutaneous low molecular weight heparin with adjusted-dose, intravenous or subcutaneous, unfractionated heparin in patients with venous thromboembolism.
Two reviewers assessed trials for inclusion and quality, and extracted data independently.
Fourteen studies with a total of 4754 patients were included. By the end of follow up in ten trials, thrombotic complications occurred in 86 (4.3%) of the 1998 patients treated with low molecular weight heparin, compared with 113 (5.6%) of the 2021 patients treated with unfractionated heparin (odds ratio 0.76, 95% confidence interval 0.57 to 1.01). In eight trials a reduction in thrombus size was shown by 60% treated with low molecular weight heparin and 54% treated with unfractionated heparin (odds ratio 0.77, 95% confidence interval 0.61 to 0.97). At the end of the initial treatment period, in all 14 of the trials, major haemorrhages occurred in 30 (1.3%) of the 2353 patients treated with low molecular weight heparin, compared with 51 (2.1%) of the 2401 patients treated with unfractionated heparin (odds ratio 0.60, 95% confidence interval 0.39 to 0.93). By the end of follow up in 11 trials, 135 (6.4%) of the 2108 patients treated with low molecular weight heparin had died, compared with 172 (8.0%) of the 2137 patients treated with unfractionated heparin (odds ratio 0.78, 95% confidence interval 0.62 to 0.99). Five studies with a total of 1636 patients examined proximal (above the knee) thrombosis; 814 treated with low molecular weight heparin and 822 with unfractionated heparin. A sub-analysis of these trials showed statistically significant reductions favouring the action of low molecular weight heparin in three areas: thrombotic complications; major haemorrhages; and overall mortality. By the end of follow up 39 (4. 8%) patients treated with low molecular weight heparin had thrombotic complications, compared with 64 (7.8%) treated with unfractionated heparin (odds ratio 0.60, 95% confidence interval 0. 40 to 0.89). Major haemorrhages occurred in 8 (1.0%) treated with low molecular weight heparin, compared with 68 (8.3%) treated with unfractionated heparin (odds ratio 0.44, 95% confidence interval 0. 21 to 0.95). By the end of follow up, 44 (5.4%) treated with low molecular weight heparin had died, compared with 68 (8.3%) treated with unfractionated heparin (odds ratio 0.64, 95% confidence interval 0.43 to 0.93).
REVIEWER'S CONCLUSIONS: Low molecular weight heparin is at least as effective as unfractionated heparin in preventing recurrent venous thromboembolism, and significantly reduces the occurrence of major haemorrhage during initial treatment and overall mortality at the end of follow-up. It can be adopted safely as the standard therapy for deep venous thrombosis, and studies comparing individual low molecular weight heparins are merited.
低分子量肝素已被证明在预防静脉血栓栓塞方面有效且安全。越来越多的证据表明，这些新型抗凝剂在治疗静脉血栓栓塞方面同样有效且安全。
本综述的目的是确定与调整剂量的静脉或皮下普通肝素相比，固定剂量皮下低分子量肝素用于急性深静脉血栓形成或肺栓塞初始治疗的效果。
从Cochrane外周血管疾病组试验注册库和拉丁美洲及加勒比地区卫生科学数据库（LILACS）中识别试验。综述作者联系了同事和制药公司代表以获取有关试验的更多信息。
比较固定剂量皮下低分子量肝素与调整剂量静脉或皮下普通肝素治疗静脉血栓栓塞患者的随机试验。
两名综述作者评估试验是否纳入及质量，并独立提取数据。
纳入了14项研究，共4754例患者。在10项试验的随访结束时，1998例接受低分子量肝素治疗的患者中有86例（4.3%）发生血栓形成并发症，而2021例接受普通肝素治疗的患者中有113例（5.6%）发生（比值比0.76，95%置信区间0.57至1.01）。在8项试验中，接受低分子量肝素治疗的患者血栓大小减少60%，接受普通肝素治疗的患者减少54%（比值比0.77，95%置信区间0.61至0.97）。在初始治疗期结束时，在所有14项试验中，2353例接受低分子量肝素治疗的患者中有30例（1.3%）发生大出血，而2401例接受普通肝素治疗的患者中有51例（2.1%）发生（比值比0.60，95%置信区间0.39至0.93）。在11项试验的随访结束时，2108例接受低分子量肝素治疗的患者中有135例（6.4%）死亡，而2137例接受普通肝素治疗的患者中有172例（8.0%）死亡（比值比0.78，95%置信区间0.62至0.99）。5项共1636例患者的研究检查了近端（膝上）血栓形成；814例接受低分子量肝素治疗，822例接受普通肝素治疗。这些试验的亚组分析显示，在三个方面低分子量肝素的作用有统计学意义的降低：血栓形成并发症；大出血；以及总死亡率。随访结束时，39例（4.8%）接受低分子量肝素治疗的患者发生血栓形成并发症，而64例（7.8%）接受普通肝素治疗的患者发生（比值比0.60，95%置信区间0.40至0.89）。8例（1.0%）接受低分子量肝素治疗的患者发生大出血，而68例（8.3%）接受普通肝素治疗的患者发生（比值比0.44，95%置信区间0.21至0.95）。随访结束时，44例（5.4%）接受低分子量肝素治疗的患者死亡，而68例（8.3%）接受普通肝素治疗的患者死亡（比值比0.64，95%置信区间0.43至0.93）。
低分子量肝素在预防复发性静脉血栓栓塞方面至少与普通肝素一样有效，并显著降低初始治疗期间大出血的发生率和随访结束时的总死亡率。它可以安全地作为深静脉血栓形成的标准治疗方法采用，比较各个低分子量肝素的研究是有价值的。
