Hull R, Raskob G, Pineo G, Rosenbloom D, Evans W, Mallory T, Anquist K, Smith F, Hughes G, Green D
Clinical Trials Unit, Faculty of Medicine, University of Calgary, Alta., Canada.
N Engl J Med. 1993 Nov 4;329(19):1370-6. doi: 10.1056/NEJM199311043291902.
Deep-vein thrombosis is a potentially life-threatening complication of total hip or knee replacement. There are few data on the effectiveness and safety of warfarin as compared with low-molecular-weight heparin as prophylaxis against this problem.
We therefore performed a randomized, double-blind trial in 1436 patients to evaluate the effectiveness and safety of low-molecular-weight heparin (given subcutaneously once daily) as compared with adjusted-dose warfarin to prevent venous thrombosis after hip or knee replacement. Treatment with the drugs was started postoperatively. The primary end point was deep-vein thrombosis as detected by contrast venography (performed a mean of 9.4 days after surgery in each group).
Among the 1207 patients with interpretable venograms, 231 of 617 patients (37.4 percent) in the warfarin group and 185 of 590 patients (31.4 percent) in the low-molecular-weight-heparin group had deep-vein thrombosis (P = 0.03). The reduction in risk with low-molecular-weight heparin as compared with warfarin was 16 percent, and the absolute difference in the incidence of venous thrombosis was 6 percent in favor of low-molecular-weight heparin (95 percent confidence interval, 0.8 to 11.4 percent). The incidence of major bleeding was 1.2 percent (9 of 721 patients) in the warfarin group and 2.8 percent (20 of 715 patients) in the low-molecular-weight-heparin group (P = 0.04), and the absolute difference was 1.5 percent in favor of warfarin (95 percent confidence interval, 0.1 to 3.0 percent).
Our data demonstrate that the small reduction in the incidence of venous thrombosis with low-molecular-weight heparin, as compared with warfarin, was offset by an increase in bleeding complications. Although the use of low-molecular-weight heparin is simpler, because it is administered subcutaneously without the need for monitoring, it may be more costly than warfarin. Warfarin is inexpensive, but the overall cost of its use is increased by the need to monitor the intensity of anticoagulation. At this time it is unclear which of these approaches is the most cost effective.
深静脉血栓形成是全髋关节或全膝关节置换术一种潜在的危及生命的并发症。与低分子量肝素相比，关于华法林预防该问题的有效性和安全性的数据较少。
因此，我们对1436例患者进行了一项随机双盲试验，以评估低分子量肝素（每日皮下注射一次）与调整剂量华法林预防髋关节或膝关节置换术后静脉血栓形成的有效性和安全性。术后开始使用这些药物进行治疗。主要终点是通过静脉造影检测到的深静脉血栓形成（每组平均在术后9.4天进行）。
在1207例可解释静脉造影结果的患者中，华法林组617例患者中有231例（37.4%）发生深静脉血栓形成，低分子量肝素组590例患者中有185例（31.4%）发生深静脉血栓形成（P = 0.03）。与华法林相比，低分子量肝素使风险降低了16%，静脉血栓形成发生率的绝对差异为6%，低分子量肝素更具优势（95%置信区间为0.8%至11.4%）。华法林组大出血发生率为1.2%（721例患者中有9例），低分子量肝素组为2.8%（715例患者中有20例）（P = 0.04），绝对差异为1.5%，华法林更具优势（95%置信区间为0.1%至3.0%）。
我们的数据表明，与华法林相比，低分子量肝素使静脉血栓形成发生率略有降低，但被出血并发症的增加所抵消。虽然使用低分子量肝素更简便，因为它皮下给药无需监测，但可能比华法林成本更高。华法林价格便宜，但由于需要监测抗凝强度，其总体使用成本增加。目前尚不清楚哪种方法最具成本效益。
