Stroke：达比加群酯致出血性卒中的发生率低于华法林

亚洲人群的颅内出血发生率高于非亚洲人群，尤其是在那些进行华法林治疗的患者。亚洲和非亚洲人群中使用达比加群酯与华法林对卒中及出血发生率的影响尚不清楚。为此，一项国际合作研究对此进行探讨，我国阜外心血管医院的朱俊教授等人参与了该项目，研究成果在线发表在2013年6月6日的Stroke杂志上。研究结果显示：在相似的血压、年龄和国际标准化比值（INR）下，亚洲人群使用华法林的出血性卒中发生率高于非亚洲人群。使用达比加群酯能够降低亚洲和非亚洲人群出血性卒中的发生率。达比加群酯的获益在亚洲和非亚洲亚组中是一致的。

研究人员共纳入10个亚洲国家的2782位患者（占总人数的15%）及34个非亚洲国家中的15331位患者。使用带“治疗、地域及它们相互作用”的Cox回归模型。

研究结果显示：在亚洲人群中，使用华法林的患者出现卒中或全身性栓塞的年发病率为3.06%，使用达比加群酯110mgbid者年发病率为2.50，达比加群酯150mg bid者年发病率为1.39%；在非亚洲人群中，以上三组数据分别为1.48%、1.37%和1.06%，且患者地域、治疗及相互作用没有显著性。华法林治疗患者中，亚洲人群发生出血性卒中的发生率高于非亚洲人群(风险比 [HR]为2.4; 95% 可信区间[CI]：1.3–4.7; P=0.007)。亚洲人群 (达比加群酯110 mg 对比华法林的HR为0.15; 95% CI：0.03–0.66 ，而达比加群酯150mg bid对比华法林HR为0.22; 95% CI：0.06–0.77)与非亚洲人群 (达比加群酯110mg bid对比华法林HR为0.37; 95% CI：0.19–0.72，而达比加群酯150mg bid对比华法林HR为0.28; 95% CI：0.13–0.58) 达比加群酯出血性卒中的发生率都低于华法林组。 在亚洲人群中，两种剂量的达比加群酯的主要出血风险均显著低于华法林组(华法林组每年3.82%, 达比加群酯组110 mg bid为每年2.22%，而150mg bid为每年2.17%)。

该研究发现：在相似的血压、年龄和国际标准化比值（INR）下，亚洲人群使用华法林的出血性卒中发生率高于非亚洲人群。使用达比加群酯能够降低亚洲和非亚洲人群出血性卒中的发生率。达比加群酯的获益在亚洲和非亚洲亚组中是一致的。

Dabigatran Versus Warfarin: Effects on Ischemic and Hemorrhagic Strokes and Bleeding in Asians and Non-Asians With Atrial Fibrillation.
BACKGROUND AND PURPOSE
Intracranial hemorrhage rates are higher in Asians than non-Asians, especially in patients receiving warfarin. This randomized evaluation of long-term anticoagulation therapy subgroup analysis assessed dabigatran etexilate (DE) and warfarin effects on stroke and bleeding rates in patients from Asian and non-Asian countries.
METHODS
There were 2782 patients (15%) from 10 Asian countries and 15 331 patients from 34 non-Asian countries. A Cox regression model, with terms for treatment, region, and their interaction was used.
RESULTS
Rates of stroke or systemic embolism in Asians were 3.06% per year on warfarin, 2.50% per year on DE 110 mg BID (DE 110), and 1.39% per year on DE 150 mg BID (DE 150); in non-Asians, the rates were 1.48%, 1.37%, and 1.06% per year with no significant treatment-by-region interactions. Hemorrhagic stroke on warfarin occurred more often in Asians than non-Asians (hazard ratio [HR], 2.4; 95% confidence interval [CI], 1.3-4.7; P=0.007), with significant reductions for DE compared with warfarin in both Asian (DE 110 versus warfarin HR, 0.15; 95% CI, 0.03-0.66 and DE 150 versus warfarin HR, 0.22; 95% CI, 0.06-0.77) and non-Asian (DE 110 versus warfarin HR, 0.37; 95% CI, 0.19-0.72 and DE 150 versus warfarin HR, 0.28; 95% CI, 0.13-0.58) patients. Major bleeding rates in Asians were significantly lower on DE (both doses) than warfarin (warfarin 3.82% per year, DE 110 2.22% per year, and DE 150 2.17% per year).
CONCLUSIONS
Hemorrhagic stroke rates were higher on warfarin in Asians versus non-Asians, despite similar blood pressure, younger age, and lower international normalized ratio values. Hemorrhagic strokes were significantly reduced by DE in both Asians and non-Asians. DE benefits were consistent across Asian and non-Asian subgroups.