Edoxaban's Journey: From East Asia to the Globe, Back to East Asia.
Edoxaban's Journey: From East Asia to the Globe, Back to East Asia.
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艾多沙班的旅程：从东亚到全球，再回到东亚。
DOI：
10.1016/j.jacc.2018.05.067
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发表时间：
2018
期刊：
影响因子：
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通讯作者：
Goto S and Goto S
中科院分区：
文献类型：
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作者：
Kato ET;Goto S;Giugliano RP;Goto S and Goto S
在本期杂志中，Lee 等人 (1) 报道了对韩国国民健康保险服务大型数据库的观察分析，显示了接受艾多沙班治疗和接受华法林治疗的非瓣膜性心房颤动 (AF) 患者之间的差异。全球 ENGAGE AF-TIMI 48（心房颤动中使用下一代 Xa 因子进行有效抗凝 - 心肌梗死溶栓 48）试验表明，与华法林相比，艾多沙班在预防中风/全身性栓塞方面具有非劣效，并且对于心血管原因引起的严重出血/死亡具有更好的安全性 (2)。然而，ENGAGE AF-TIMI 48 试验仅包括少数东亚受试者。 Lee等人的数据提供了在区域“现实世界”环境中验证全球试验结果的重要机会。由于人们认为东亚患者在抗凝剂的使用方面与其他患者群体不同，因此对东亚全球试验进行此类区域验证非常重要。这种强烈的认知甚至影响了日本直接口服抗凝药 (DOAC) 的开发，也影响了 J-ROCKETAF（利伐沙班预防非瓣膜性心房颤动受试者中风的功效和安全性；NCT00494871）研究 (3) 中对 70 岁以上老年受试者的单独分析（3）与使用目标凝血酶原的华法林相比，使用减少剂量的利伐沙班治疗时间-国际标准化比率为 1.6 至 2.0，不在 ROCKET-AF（利伐沙班联合华法林预防非瓣膜性房颤患者中风和非中枢神经系统系统性栓塞的功效和安全性研究；NCT00403767）试验之外 (4)。小样本的区域随机试验没有为全球护理标准的改变提供强有力的科学证据。 Lee 等人 (1) 使用观察数据对全球试验结果进行区域验证，是克服全球人群中潜在异质性的一种方法 (5)。Lee 等人 (1) 在分析艾多沙班治疗和华法林治疗患者之间的比较方面所做的巨大努力值得赞扬。由于韩国人口代表性超过 97%，他们的数据应反映韩国的“现实世界”实践。然而，他们的分析在艾多沙班和华法林的比较方面存在一些重要的局限性。 Lee 等人(1) 首先对 648,560 名患有 AF 的患者进行了研究。排除绝大多数患者，以实现一级预防队列中 35,765 名华法林或艾多沙班新使用者的最终比较。尽管之前的出版物使用同一韩国国家数据库表明 DOAC 具有更好的疗效和安全性 (6)，但值得注意的是，艾多沙班是处方最少的 DOAC（艾多沙班 4,200；达比加群 14,375；利伐沙班 22,968；阿哌沙班 12,657）。医生的选择并非基于常用的风险分层工具，例如 CHA2DS2-VASc（充血性心力衰竭、高血压、年龄 75 岁以上、糖尿病、既往中风、短暂性脑缺血发作或血栓栓塞、血管疾病、年龄 65-74 岁、性别类别
In this issue of the Journal, Lee et al.(1) reported an observational analysis of the large Korean National Health Insurance Service database showing the difference between edoxaban-treated and warfarin-treated patients with nonvalvular atrial fibrillation (AF). The noninferior efficacy of edoxaban for prevention of stroke/systemic embolism and its better safety for serious bleeding/mortality from cardiovascular causes, as compared with warfarin, were shown by the global ENGAGE AF-TIMI 48 (Effective Anticoagulation with Factor Xa Next Generation in Atrial Fibrillation–Thrombolysis In Myocardial Infarction 48) trial (2). However, the ENGAGE AF-TIMI 48 trial only included a small number of East Asian subjects. Lee et al.’s data provide an important opportunity to validate the global trial results in a regional “real-world” setting. This type of regional validation of global trials in East Asia is important due to the perception that East Asian patients differ from other patient populations with regard to the use of anticoagulants. This strong perception—even influencing direct oral anticoagulant (DOAC) development in Japan—also affected the separate analysis in elderly subjects more than 70 years of age in the J-ROCKETAF (Efficacy and Safety of Rivaroxaban for the Prevention of Stroke in Subjects With Non-Valvular Atrial Fibrillation; NCT00494871) study (3) treated with a reduced dose of rivaroxaban versus warfarin with a target prothrombin time–international normalized ratio of 1.6 to 2.0, which was outside of the ROCKET-AF (An Efficacy and Safety Study of Rivaroxaban With Warfarin for the Prevention of Stroke and Non-Central Nervous System Systemic Embolism in Patients With Non-Valvular Atrial Fibrillation; NCT00403767) trial (4). Regional randomized trials with small sample sizes did not provide strong scientific evidence for changing in the standard of care around the globe. Regional validation of global trial results with observatory data, as conducted by Lee et al.(1), is one way to overcome potential heterogeneity within the worldwide population (5).The huge effort by Lee et al.(1) to analyze the comparison between edoxaban-treated and warfarintreated patients should be commended. Their data should reflect “real-world” practice in Korea due to> 97% population representation. However, their analysis contains several important limitations with regard to the comparison of edoxaban and warfarin. Lee et al.(1) started with a large population of 648,560 patients with prevalent AF. The vast majority of patients were excluded to achieve the final comparison of 35,765 new users of either warfarin or edoxaban in a primary prevention cohort. Although there are previous publications that had suggested better efficacy and safety of DOACs using the same Korean national database (6), it is of note that edoxaban was the least prescribed DOAC (edoxaban 4,200; dabigatran 14,375; rivaroxaban 22,968; apixaban 12,657). Physicians’ choices were not based on commonly used risk stratification tools such as the CHA2DS2-VASc (congestive heart failure, hypertension, age $75 years, diabetes mellitus, prior stroke, transient ischemic attack, or thromboembolism, vascular disease, age 65–74 years, sex category