Wang Kang-Ling, Lip Gregory Y H, Lin Shing-Jong, Chiang Chern-En
From the General Clinical Research Center (K.-L.W., C.-E.C.), Department of Medical Research (K.-L.W., S.-J.L., C.-E.C.), and Division of Cardiology (K.-L.W., S.-J.L., C.-E.C.), Taipei Veterans General Hospital, Taipei, Taiwan; School of Medicine, National Yang-Ming University, Taipei, Taiwan (K.-L.W., S.-J.L., C.-E.C.); University of Birmingham, Centre for Cardiovascular Sciences, City Hospital, Birmingham, United Kingdom (G.Y.H.L.); and Aalborg Thrombosis Research Unit, Department of Clinical Medicine, Aalborg University, Aalborg, Denmark (G.Y.H.L.).
Stroke. 2015 Sep;46(9):2555-61. doi: 10.1161/STROKEAHA.115.009947. Epub 2015 Jul 30.
The use of vitamin K antagonists (VKAs), the cornerstone treatment for stroke prevention in patients with atrial fibrillation, is limited by the perceived risk of serious bleeding in Asia. Non-VKA oral anticoagulants (NOACs) are safer alternatives. Here, we evaluate performance differences of NOACs between Asians and non-Asians.
We compared efficacy and safety of NOACs between patients enrolled in Asian and non-Asian countries using aggregative data from phase III clinical trials. The odds ratios (ORs [95% confidence interval]) were calculated by a random effects model.
Comparing with VKAs, standard-dose NOACs reduced stroke or systemic embolism (OR=0.65 [0.52-0.83] versus 0.85 [0.77-0.93], P interaction= 0.045) more in Asians than in non-Asians and were safer in Asians than in non-Asians about major bleeding (OR=0.57 [0.44-0.74] versus 0.89 [0.76-1.04], P interaction=0.004), hemorrhagic stroke (OR=0.32 [0.19-0.52] versus 0.56 [0.44-0.70], P interaction=0.046) in particular, whereas gastrointestinal bleeding was significantly increased in non-Asians (OR=0.79 [0.48-1.32] versus 1.44 [1.12-1.85], P interaction=0.041). Generally, low-dose NOACs were safer than VKAs without heterogeneity in efficacy and safety between Asians and non-Asians, except for ischemic stroke, major, and gastrointestinal bleeding.
Our findings suggest that standard-dose NOACs were more effective and safer in Asians than in non-Asians, whereas low-dose NOACs performed similarly in both populations.
维生素K拮抗剂(VKAs)作为心房颤动患者预防卒中的基础治疗方法,在亚洲因严重出血风险而应用受限。非维生素K拮抗剂口服抗凝药(NOACs)是更安全的替代药物。在此,我们评估亚洲人与非亚洲人使用NOACs的疗效差异。
我们利用Ⅲ期临床试验的汇总数据,比较了亚洲和非亚洲国家入组患者使用NOACs的疗效和安全性。采用随机效应模型计算比值比(ORs[95%置信区间])。
与VKAs相比,标准剂量的NOACs在亚洲人中比在非亚洲人中更能降低卒中或全身性栓塞(OR=0.65[0.52-0.83] vs 0.85[0.77-0.93],P交互作用=0.045),且在亚洲人中比在非亚洲人中更安全(主要出血方面:OR=0.57[0.44-0.74] vs 0.89[0.76-1.04],P交互作用=0.004;尤其是出血性卒中方面:OR=0.32[0.19-0.52] vs 0.56[0.44-0.70],P交互作用=0.046),而胃肠道出血在非亚洲人中显著增加(OR=0.79[0.48-1.32] vs 1.44[1.12-1.85],P交互作用=0.041)。总体而言,低剂量NOACs比VKAs更安全,在亚洲人和非亚洲人中的疗效和安全性无差异,但缺血性卒中、主要出血和胃肠道出血除外。
我们的研究结果表明,标准剂量的NOACs在亚洲人中比在非亚洲人中更有效、更安全,而低剂量NOACs在这两个人群中的表现相似。