Population Health Research Institute, McMaster University and Hamilton Health Sciences, Hamilton, Ontario, Canada.
Stroke. 2012 Jun;43(6):1511-7. doi: 10.1161/STROKEAHA.112.650614. Epub 2012 Apr 5.
Intracranial hemorrhage is the most devastating complication of anticoagulation. Outcomes associated with different sites of intracranial bleeding occurring with warfarin versus dabigatran have not been defined.
Analysis of 18 113 participants with atrial fibrillation in the Randomized Evaluation of Long-term anticoagulant therapY (RE-LY) trial assigned to adjusted-dose warfarin (target international normalized ratio, 2-3) or dabigatran (150 mg or 110 mg, both twice daily).
During a mean of 2.0 years of follow-up, 154 intracranial hemorrhages occurred in 153 participants: 46% intracerebral (49% mortality), 45% subdural (24% mortality), and 8% subarachnoid (31% mortality). The rates of intracranial hemorrhage were 0.76%, 0.31%, and 0.23% per year among those assigned to warfarin, dabigatran 150 mg, and dabigatran 110 mg, respectively (P<0.001 for either dabigatran dose versus warfarin). Fewer fatal intracranial hemorrhages occurred among those assigned dabigatran 150 mg and 110 mg (n=13 and n=11, respectively) versus warfarin (n=32; P<0.01 for both). Fewer traumatic intracranial hemorrhages occurred among those assigned to dabigatran (11 patients with each dose) compared with warfarin (24 patients; P<0.05 for both dabigatran doses versus warfarin). Independent predictors of intracranial hemorrhage were assignment to warfarin (relative risk, 2.9; P<0.001), aspirin use (relative risk, 1.6; P=0.01), age (relative risk, 1.1 per year; P<0.001), and previous stroke/transient ischemic attack (relative risk, 1.8; P=0.001).
The clinical spectrum of intracranial hemorrhage was similar for patients given warfarin and dabigatran. Absolute rates at all sites and both fatal and traumatic intracranial hemorrhages were lower with dabigatran than with warfarin. Concomitant aspirin use was the most important modifiable independent risk factor for intracranial hemorrhage.
颅内出血是抗凝治疗最具破坏性的并发症。华法林和达比加群导致的颅内不同部位出血的相关结局尚未明确。
对随机评估长期抗凝治疗（RE-LY）试验中的 18113 名房颤患者进行分析，这些患者被分配至调整剂量华法林（目标国际标准化比值 2-3）或达比加群（150 mg 或 110 mg，每日 2 次）。
在平均 2.0 年的随访期间，153 名患者中发生 154 例颅内出血：46%为脑内（49%死亡率），45%为硬膜下（24%死亡率），8%为蛛网膜下腔（31%死亡率）。接受华法林、达比加群 150 mg 和达比加群 110 mg 治疗的患者颅内出血发生率分别为 0.76%、0.31%和 0.23%/年（达比加群任一剂量与华法林相比，P<0.001）。与华法林（n=32）相比，接受达比加群 150 mg 和 110 mg 治疗的患者发生致命性颅内出血的人数更少（分别为 n=13 和 n=11；P<0.01）。与华法林（n=24）相比，接受达比加群治疗的患者发生创伤性颅内出血的人数更少（各剂量组均为 11 例；P<0.05）。颅内出血的独立预测因素包括接受华法林治疗（相对风险 2.9；P<0.001）、使用阿司匹林（相对风险 1.6；P=0.01）、年龄（相对风险每年增加 1.1；P<0.001）和既往卒中和短暂性脑缺血发作（相对风险 1.8；P=0.001）。
接受华法林和达比加群治疗的患者颅内出血的临床谱相似。达比加群的所有部位、致命性和创伤性颅内出血的绝对发生率均低于华法林。同时使用阿司匹林是颅内出血最重要的可改变的独立危险因素。
