Department of Hematology, Lahey Clinic, Burlington, MA 01805, USA.
Thromb Haemost. 2012 Sep;108(3):476-84. doi: 10.1160/TH12-02-0093. Epub 2012 Jun 28.
New oral anticoagulant drugs are emerging as alternatives to warfarin for the prevention of stroke in patients with non-valvular atrial fibrillation. Two agents are direct factor Xa inhibitors (rivaroxaban and apixaban), and the third is a direct thrombin inhibitor (dabigatran). They have been separately compared to warfarin in large randomised trials. Our objective was to indirectly compare the three agents to each other for major efficacy and safety outcomes. Studies were assessed for comparability and the odds ratios of selected outcomes for each anticoagulant versus one another were estimated indirectly. The three cohorts differed significantly in terms of CHADS(2) score and the number of individuals with a past history of stroke, transient ischemic attack or systemic embolism. The estimated odds ratio of stroke or systemic embolism was 1.35 for rivaroxaban vs dabigatran 150 mg (p=0.04), 0.97 for rivaroxaban versus dabigatran 110 mg (p=0.81), 1.22 for apixaban versus dabigatran 150 mg (p=0.18), 0.88 for apixaban versus dabigatran 110 mg (p=0.34) and 0.90 for apixaban versus rivaroxaban (p=0.43). The estimated odds ratio of major bleeding was 1.10 for rivaroxaban versus dabigatran 150 mg (p=0.36), 1.28 for rivaroxaban versus dabigatran 110 mg (p=0.02), 0.74 for apixaban versus dabigatran 150 mg (p=0.004), 0.87 for apixaban versus dabigatran 110 mg (p=0.17) and 0.68 for apixaban versus rivaroxaban (p<0.001). In conclusion, the available data indicate no significant difference in efficacy between dabigatran 150 mg and apixaban for the prevention of stroke or systemic embolism in patients with non-valvular atrial fibrillation. It appears however that apixaban is associated with less major bleeding than dabigatran 150 mg or rivaroxaban and that rivaroxaban is less effective than dabigatran 150 mg in preventing stroke or systemic embolism. Such an indirect comparison should be used only to generate hypotheses which need to be tested in a dedicated randomised trial comparing the three drugs directly.
新型口服抗凝药物正逐渐成为非瓣膜性心房颤动患者预防中风的华法林替代药物。两种药物是直接 Xa 因子抑制剂（利伐沙班和阿哌沙班），第三种是直接凝血酶抑制剂（达比加群）。它们已分别在大型随机试验中与华法林进行了比较。我们的目标是间接比较这三种药物在主要疗效和安全性结局方面的相互作用。评估了研究的可比性，并间接估计了每种抗凝剂与其他抗凝剂之间选定结局的比值比。三个队列在 CHADS（2）评分和过去中风、短暂性脑缺血发作或全身性栓塞史的个体数量方面存在显著差异。利伐沙班与达比加群 150mg 的中风或全身性栓塞的估计比值比为 1.35（p=0.04），利伐沙班与达比加群 110mg 的比值比为 0.97（p=0.81），阿哌沙班与达比加群 150mg 的比值比为 1.22（p=0.18），阿哌沙班与达比加群 110mg 的比值比为 0.88（p=0.34），阿哌沙班与利伐沙班的比值比为 0.90（p=0.43）。利伐沙班与达比加群 150mg 的大出血的估计比值比为 1.10（p=0.36），利伐沙班与达比加群 110mg 的比值比为 1.28（p=0.02），阿哌沙班与达比加群 150mg 的比值比为 0.74（p=0.004），阿哌沙班与达比加群 110mg 的比值比为 0.87（p=0.17），阿哌沙班与利伐沙班的比值比为 0.68（p<0.001）。总之，现有数据表明，在预防非瓣膜性心房颤动患者中风或全身性栓塞方面，达比加群 150mg 与阿哌沙班之间的疗效无显著差异。然而，阿哌沙班似乎比达比加群 150mg 或利伐沙班引起的大出血更少，而利伐沙班预防中风或全身性栓塞的效果不如达比加群 150mg。这种间接比较仅应用于产生假说，这些假说需要在直接比较三种药物的专门随机试验中进行检验。
