Population Health Research Institute, Hamilton Health Sciences and McMaster University, Hamilton, Ontario, Canada.
Circulation. 2011 May 31;123(21):2363-72. doi: 10.1161/CIRCULATIONAHA.110.004747. Epub 2011 May 16.
Dabigatran 150 and 110 mg twice a day and warfarin are effective for stroke prevention in atrial fibrillation. The purpose of this study was to compare their risks of bleeding in the Randomized Evaluation of Long-Term Anticoagulant Therapy (RE-LY) trial.
The RE-LY trial randomized 18 113 patients to receive dabigatran 110 or 150 mg twice a day or warfarin dose adjusted to an international normalized ratio of 2.0 to 3.0 for a median follow-up of 2.0 years. Compared with warfarin, dabigatran 110 mg twice a day was associated with a lower risk of major bleeding (2.87% versus 3.57%; P=0.002), whereas dabigatran 150 mg twice a day was associated with a similar risk of major bleeding (3.31% versus 3.57%; P=0.32). There was a significant treatment-by-age interaction, such that dabigatran 110 mg twice a day compared with warfarin was associated with a lower risk of major bleeding in patients aged <75 years (1.89% versus 3.04%; P<0.001) and a similar risk in those aged ≥75 years (4.43% versus 4.37%; P=0.89; P for interaction <0.001), whereas dabigatran 150 mg twice a day compared with warfarin was associated with a lower risk of major bleeding in those aged <75 years (2.12% versus 3.04%; P<0.001) and a trend toward higher risk of major bleeding in those aged ≥75 years (5.10% versus 4.37%; P=0.07; P for interaction <0.001). The interaction with age was evident for extracranial bleeding, but not for intracranial bleeding, with the risk of the latter being consistently reduced with dabigatran compared with warfarin irrespective of age.
In patients with atrial fibrillation at risk for stroke, both doses of dabigatran compared with warfarin have lower risks of both intracranial and extracranial bleeding in patients aged <75 years. In those aged ≥75 years, intracranial bleeding risk is lower but extracranial bleeding risk is similar or higher with both doses of dabigatran compared with warfarin.
http://www.clinicaltrials.gov. Unique identifier: NCT00262600.
达比加群 150 毫克和 110 毫克，每日两次，以及华法林均可有效预防房颤患者发生卒中。本研究旨在比较这两种药物在随机评价长期抗凝治疗（RE-LY）试验中的出血风险。
RE-LY 试验将 18113 例患者随机分为达比加群 110 毫克，每日两次，或达比加群 150 毫克，每日两次，或华法林组（调整国际标准化比值至 2.0~3.0），中位随访时间为 2.0 年。与华法林相比，达比加群 110 毫克，每日两次治疗组大出血风险较低（2.87% vs. 3.57%；P=0.002），而达比加群 150 毫克，每日两次治疗组大出血风险相似（3.31% vs. 3.57%；P=0.32）。存在治疗与年龄的交互作用，提示达比加群 110 毫克，每日两次治疗组与华法林相比，在年龄<75 岁的患者中出血风险较低（1.89% vs. 3.04%；P<0.001），在年龄≥75 岁的患者中出血风险相似（4.43% vs. 4.37%；P=0.89；P 值<0.001），而达比加群 150 毫克，每日两次治疗组与华法林相比，在年龄<75 岁的患者中出血风险较低（2.12% vs. 3.04%；P<0.001），在年龄≥75 岁的患者中出血风险有升高趋势（5.10% vs. 4.37%；P=0.07；P 值<0.001）。这种与年龄的交互作用在颅外出血中明显，但在颅内出血中不明显，与华法林相比，达比加群始终降低颅内出血风险。
在存在卒中风险的房颤患者中，与华法林相比，达比加群的两种剂量均能降低年龄<75 岁患者的颅内和颅外出血风险。对于年龄≥75 岁的患者，颅内出血风险较低，但达比加群的两种剂量均使颅外出血风险相似或升高。
