Russell D. Hull, Thrombosis Research Unit, University of Calgary, Foothills Hospital, Room 906 South Tower, 1403 29th Street NW, Calgary, AB T2N 2T9, Canada, Tel.: +1 403 944 8047, Fax: +1 403 270 7891, E-mail:
Thromb Haemost. 2014 Feb;111(2):199-212. doi: 10.1160/TH13-08-0654. Epub 2013 Oct 24.
Surgeons consider the benefit-to-harm ratio when making decisions regarding the use of anticoagulant venous thromboembolism (VTE) prophylaxis. We evaluated the benefit-to-harm ratio of the use of newer anticoagulants as thromboprophylaxis in patients undergoing major orthopaedic surgery using the likelihood of being helped or harmed (LHH), and assessed the effects of variation in the definition of major bleeding on the results. A systematic literature search was performed to identify phase II and phase III studies that compared regulatory authority-approved newer anticoagulants to the low-molecular-weight heparin enoxaparin in patients undergoing major orthopaedic surgery. Analysis of outcomes data estimated the clinical benefit (number-needed-to-treat [NNT] to prevent one symptomatic VTE) and clinical harm (number-needed-to-harm [NNH] or the NNT to cause one major bleeding event) of therapies. We estimated each trial's benefit-to-harm ratio from NNT and NNH values, and expressed this as LHH = (1/NNT)/(1/NNH) = NNH/NNT. Based on reporting of efficacy and safety outcomes, most studies favoured enoxaparin over fondaparinux, and rivaroxaban over enoxaparin. However, when using the LHH metric, most trials favoured enoxaparin over both fondaparinux and rivaroxaban when they included surgical-site bleeding that did not require reoperation in the definition of major bleeding. The exclusion of bleeding at surgical site which did not require reoperation shifted the benefit-to-harm ratio in favour of the newer agents. Variations in the definitions of major bleeding may change the benefit-to-harm ratio and subsequently affect its interpretation. Clinical trials should attempt to improve the consistency of major bleeding reporting.
外科医生在决定是否使用抗凝药物预防静脉血栓栓塞症（VTE）时，会考虑获益与危害的比值。我们使用获益与危害比值（LHH）评估了新型抗凝药物在接受大型骨科手术的患者中作为血栓预防药物的获益与危害比值，并评估了主要出血定义的变化对结果的影响。我们进行了系统的文献检索，以确定比较新型抗凝药物与监管机构批准的低分子量肝素依诺肝素在接受大型骨科手术的患者中的疗效的 II 期和 III 期研究。对结局数据的分析估计了治疗的临床获益（预防 1 例有症状 VTE 的所需治疗人数[NNT]）和临床危害（导致 1 例大出血事件的所需治疗人数[NNH]或 NNT 导致 1 例大出血事件的 NNH）。我们根据 NNT 和 NNH 值估计每个试验的获益与危害比值，并表示为 LHH =（1/NNT）/（1/NNH）= NNH/NNT。根据疗效和安全性结局的报告，大多数研究表明依诺肝素优于磺达肝素，利伐沙班优于依诺肝素。然而，当使用 LHH 指标时，当将需要再次手术的手术部位出血纳入大出血定义时，大多数试验都表明依诺肝素优于磺达肝素和利伐沙班。不包括不需要再次手术的手术部位出血的出血会使获益与危害比值偏向新型药物。大出血定义的变化可能会改变获益与危害比值，进而影响其解释。临床试验应努力提高大出血报告的一致性。
