Quantitative Solutions, Inc., Menlo Park, California, USA.
Clin Pharmacol Ther. 2011 Dec;90(6):820-7. doi: 10.1038/clpt.2011.232. Epub 2011 Nov 2.
Information on the comparative effectiveness of drugs is crucial for drug development decisions, in addition to being needed by regulators, prescribers, and payers. We have carried out a dose-response meta-analysis of three end points each for efficacy and bleeding for various anticoagulants evaluated for the prevention of venous thromboembolism (VTE) following orthopedic surgery to assess the comparative efficacy and safety of various classes of agents. Data obtained from 89 randomized controlled trials of 23 anticoagulants representing seven drug classes were analyzed. The analysis showed significant differences in the therapeutic index (TI), the ratio of the dose with an acceptable bleeding risk to the dose with a relevant risk reduction for VTE, across the drug classes but not for drugs within a class. The direct inhibitors of FXa, the activated form of factor X--also known as prothrombinase--were found to have a significantly higher TI than that of any other class of anticoagulants, including enoxaparin, suggesting that this mechanism of action provides the best safety-to-efficacy margin.
药物疗效的相关信息对药物研发决策至关重要，此外，监管机构、处方医生和支付方也需要这些信息。我们针对各种骨科手术后预防静脉血栓栓塞症（VTE）的抗凝药物进行了疗效和出血各三个终点的剂量反应荟萃分析，以评估各种药物类别的相对疗效和安全性。分析中纳入了 89 项随机对照试验，涉及 23 种抗凝药物，涵盖了 7 个药物类别。结果显示，不同药物类别之间的治疗指数（TI）存在显著差异，即具有可接受出血风险的剂量与具有相关 VTE 风险降低的剂量之比存在差异，但同一药物类别内的药物之间不存在差异。直接 FXa 抑制剂，即因子 X 的激活形式（也称为凝血酶原酶），其 TI 明显高于任何其他类别的抗凝药物，包括依诺肝素，这表明这种作用机制提供了最佳的安全性-疗效边际。
