Connolly Stuart J, Ezekowitz Michael D, Yusuf Salim, Eikelboom John, Oldgren Jonas, Parekh Amit, Pogue Janice, Reilly Paul A, Themeles Ellison, Varrone Jeanne, Wang Susan, Alings Marco, Xavier Denis, Zhu Jun, Diaz Rafael, Lewis Basil S, Darius Harald, Diener Hans-Christoph, Joyner Campbell D, Wallentin Lars
Population Health Research Institute, McMaster University and Hamilton Health Sciences, Hamilton, ON, Canada.
N Engl J Med. 2009 Sep 17;361(12):1139-51. doi: 10.1056/NEJMoa0905561. Epub 2009 Aug 30.
Warfarin reduces the risk of stroke in patients with atrial fibrillation but increases the risk of hemorrhage and is difficult to use. Dabigatran is a new oral direct thrombin inhibitor.
In this noninferiority trial, we randomly assigned 18,113 patients who had atrial fibrillation and a risk of stroke to receive, in a blinded fashion, fixed doses of dabigatran--110 mg or 150 mg twice daily--or, in an unblinded fashion, adjusted-dose warfarin. The median duration of the follow-up period was 2.0 years. The primary outcome was stroke or systemic embolism.
Rates of the primary outcome were 1.69% per year in the warfarin group, as compared with 1.53% per year in the group that received 110 mg of dabigatran (relative risk with dabigatran, 0.91; 95% confidence interval [CI], 0.74 to 1.11; P<0.001 for noninferiority) and 1.11% per year in the group that received 150 mg of dabigatran (relative risk, 0.66; 95% CI, 0.53 to 0.82; P<0.001 for superiority). The rate of major bleeding was 3.36% per year in the warfarin group, as compared with 2.71% per year in the group receiving 110 mg of dabigatran (P=0.003) and 3.11% per year in the group receiving 150 mg of dabigatran (P=0.31). The rate of hemorrhagic stroke was 0.38% per year in the warfarin group, as compared with 0.12% per year with 110 mg of dabigatran (P<0.001) and 0.10% per year with 150 mg of dabigatran (P<0.001). The mortality rate was 4.13% per year in the warfarin group, as compared with 3.75% per year with 110 mg of dabigatran (P=0.13) and 3.64% per year with 150 mg of dabigatran (P=0.051).
In patients with atrial fibrillation, dabigatran given at a dose of 110 mg was associated with rates of stroke and systemic embolism that were similar to those associated with warfarin, as well as lower rates of major hemorrhage. Dabigatran administered at a dose of 150 mg, as compared with warfarin, was associated with lower rates of stroke and systemic embolism but similar rates of major hemorrhage. (ClinicalTrials.gov number, NCT00262600.)
华法林可降低心房颤动患者的中风风险，但会增加出血风险且使用不便。达比加群是一种新型口服直接凝血酶抑制剂。
在这项非劣效性试验中，我们将18113例有中风风险的心房颤动患者随机分组，一组接受盲法固定剂量的达比加群（每日两次，每次110毫克或150毫克），另一组接受非盲法调整剂量的华法林。随访期的中位数为2.0年。主要结局是中风或全身性栓塞。
华法林组主要结局的发生率为每年1.69%，接受110毫克达比加群的组为每年1.53%（达比加群的相对风险为0.91；95%置信区间[CI]为0.74至1.11；非劣效性P<0.001），接受150毫克达比加群的组为每年1.11%（相对风险为0.66；95%CI为0.53至0.82；优效性P<0.001）。华法林组严重出血的发生率为每年3.36%，接受110毫克达比加群的组为每年2.71%（P=0.003），接受150毫克达比加群的组为每年3.11%（P=0.31）。华法林组出血性中风的发生率为每年0.38%，110毫克达比加群组为每年0.12%（P<0.001），150毫克达比加群组为每年0.10%（P<0.001）。华法林组的死亡率为每年4.13%，110毫克达比加群组为每年3.75%（P=0.13），150毫克达比加群组为每年3.64%（P=0.051）。
在心房颤动患者中，给予110毫克剂量的达比加群，其中风和全身性栓塞发生率与华法林相似，但严重出血发生率较低。与华法林相比，给予150毫克剂量的达比加群，其中风和全身性栓塞发生率较低，但严重出血发生率相似。（临床试验.gov编号，NCT00262600。）
