Wang Kang-Ling, Chiu Chun-Chih, Giugliano Robert P, Tan Doreen Su-Yin, Lin Chun-Yi, Lai En-Yu, Goto Shinya, Chiang Chern-En
General Clinical Research Center, Taipei Veterans General Hospital, Taipei, Taiwan; School of Medicine, National Yang-Ming University, Taipei, Taiwan.
School of Medicine, National Yang-Ming University, Taipei, Taiwan.
J Stroke Cerebrovasc Dis. 2018 Apr;27(4):857-864. doi: 10.1016/j.jstrokecerebrovasdis.2017.10.027. Epub 2017 Nov 26.
Direct oral anticoagulants (DOACs) have a better risk benefit profile in Asian patients with atrial fibrillation (AF). Whether treatment effects could be modified by drug class and dependency on renal elimination of studied agents has not yet been explored.
We searched PubMed, CENTRAL, and CINAHL databases through November 2016 for phase III randomized controlled trials comparing DOACs with warfarin in patients with AF. Efficacy and safety outcomes were pooled according to drug class and dependency on renal elimination of DOACs and were compared with the Mantel-Haenszel fixed-effects model. Effect differences were assessed with Bucher's indirect comparisons using common estimates, once heterogeneity was low, and with the Bayesian method.
Among 6496 Asian patients from 6 trials, both direct thrombin inhibitors and factor Xa inhibitors, compared with warfarin, were associated with lower risks of stroke or systemic embolism and major bleeding (risk ratio [95% confidence interval], 0.51 [0.33-0.78], 0.74 ([0.58-0.96], 0.60 [0.41-0.86], and 0.59 [0.47-0.76], respectively). There was no between-group difference in direct thrombin inhibitors and factor Xa inhibitors or in DOACs with renal elimination less than 50% and 50% or greater (all I < 25% and interaction P > .05). Indirect comparisons within strata of drug class and dependency on renal elimination showed no preferential effect of any given regimen over another. There was no difference in effects on ischemic and hemorrhagic stroke, intracranial hemorrhage, myocardial infarction, and all-cause mortality between DOACs stratified by pharmacologic characteristics.
DOACs, as a therapeutic class, outperform warfarin in efficacy and safety in Asian patients with AF.
直接口服抗凝剂（DOACs）在亚洲房颤（AF）患者中具有更好的风险效益比。药物类别以及所研究药物对肾脏清除的依赖性是否会改变治疗效果尚未得到探讨。
我们检索了截至2016年11月的PubMed、CENTRAL和CINAHL数据库，以查找在房颤患者中比较DOACs与华法林的III期随机对照试验。根据药物类别以及DOACs对肾脏清除的依赖性汇总疗效和安全性结果，并与Mantel-Haenszel固定效应模型进行比较。一旦异质性较低，使用通用估计值通过Bucher间接比较评估效应差异，并采用贝叶斯方法。
在来自6项试验的6496名亚洲患者中，与华法林相比，直接凝血酶抑制剂和Xa因子抑制剂均与较低的中风或全身性栓塞风险以及大出血风险相关（风险比[95%置信区间]分别为0.51[0.33 - 0.78]、0.74([0.58 - 0.96]、0.60[0.41 - 0.86]和0.59[0.47 - 0.76]）。直接凝血酶抑制剂和Xa因子抑制剂之间，或肾脏清除率低于50%和50%及以上的DOACs之间，组间无差异（所有I²<25%且交互P>0.05）。在药物类别和对肾脏清除的依赖性分层内的间接比较显示，任何给定方案均无优于其他方案的优先效应。按药理学特征分层的DOACs对缺血性和出血性中风、颅内出血、心肌梗死和全因死亡率的影响无差异。
作为一类治疗药物，DOACs在亚洲房颤患者的疗效和安全性方面优于华法林。
