Gärdlund B
Section of Infectious Diseases, Karolinska Hospital, Stockholm, Sweden.
Lancet. 1996 May 18;347(9012):1357-61. doi: 10.1016/s0140-6736(96)91009-0.
Fatal pulmonary embolism and other thromboembolic complications are common in hospital inpatients. However, there is little evidence on the routine use of pharmacological thromboprophylaxis in non-surgical patients. We assessed the efficacy and safety of low-dose heparin in the prevention of hospital-acquired, clinically relevant, fatal pulmonary embolism in patients with infectious diseases.
Our study used the postrandomisation consent design. 19,751 consecutive patients, aged 55 years or older, admitted to departments of infectious diseases in six Swedish hospitals, were screened for inclusion in the randomised, controlled, unblinded, multicentre trial. Of the eligible patients, 5776 were assigned subcutaneous standard heparin (5000 IU every 12 h) until hospital discharge or for a maximum of 3 weeks; 5917 were assigned no prophylactic treatment (control group). We sought consent only from the heparin group. Follow-up was for 3 weeks after discharge from hospital or for a maximum of 60 days from randomisation. The primary endpoint was necropsy-verified pulmonary embolism of predefined clinical relevance.
By intention-to-treat analysis mortality was similar in the heparin and control groups (5.3 vs 5.6%, p = 0.39) and the median time from admission to death was 16 days in both groups (IQR 8-31 vs 6-28 days). Necropsy-verified pulmonary embolism occurred in 15 heparin-treated and 16 control-group patients. There was a significant difference between heparin and control groups in median time from randomisation to fatal pulmonary embolism (28 [24-36] vs 12.5 [10-20] days, p = 0.007). This difference corresponds to the duration of heparin prophylaxis. Non-fatal thromboembolic complications occurred in more of the control than of the heparin group (116 vs 70, p = 0.0012).
Our findings do not support the routine use of heparin prophylaxis for 3 weeks or less in large groups of non-surgical patients. Further studies are needed to investigate whether heparin prophylaxis of longer duration may prevent fatal pulmonary embolism.
致命性肺栓塞及其他血栓栓塞并发症在医院住院患者中很常见。然而，关于非手术患者常规使用药物性血栓预防措施的证据很少。我们评估了低剂量肝素预防传染病患者医院获得性、临床相关的致命性肺栓塞的疗效和安全性。
我们的研究采用随机化后同意设计。对瑞典六家医院传染病科收治的19751例年龄在55岁及以上的连续患者进行筛选，以纳入随机、对照、非盲、多中心试验。在符合条件的患者中，5776例被分配皮下注射标准肝素（每12小时5000 IU）直至出院或最长3周；5917例被分配不进行预防性治疗（对照组）。我们仅向肝素组寻求同意。随访在出院后3周或随机分组后最长60天进行。主要终点是经尸检证实的具有预定义临床相关性的肺栓塞。
按意向性分析，肝素组和对照组的死亡率相似（5.3%对5.6%，p = 0.39），两组从入院到死亡的中位时间均为16天（四分位间距8 - 31天对6 - 28天）。经尸检证实的肺栓塞在15例肝素治疗患者和1例对照组患者中发生。肝素组和对照组从随机分组到致命性肺栓塞的中位时间有显著差异（28[24 - 36]天对12.5[10 - 20]天，p = 0.007）。这种差异与肝素预防的持续时间相对应。非致命性血栓栓塞并发症在对照组比肝素组更多见（116例对70例，p = 0.0012）。
我们的研究结果不支持在大量非手术患者中常规使用肝素预防3周或更短时间。需要进一步研究来调查更长时间的肝素预防是否可预防致命性肺栓塞。
