Oral anticoagulants (OACs) are commonly used to reduce the risk of venous thromboembolism and the risk of stroke in patients with atrial fibrillation. Endorsed by the American Heart Association, American College of Cardiology, and the European Society of Cardiology, direct oral anticoagulants (DOACs) have displaced warfarin as the OAC of choice for both conditions, due to improved safety profiles, fewer drug–drug and drug–diet interactions, and lack of monitoring requirements. Despite their widespread use and improved safety over warfarin, DOAC-related bleeding remains a major concern for patients. DOACs have stable pharmacokinetics and pharmacodynamics; however, variability in DOAC response is common and may be attributed to numerous factors, including patient-specific factors, concomitant medications, comorbid conditions, and genetics. Although DOAC randomized controlled trials included patients of varying ages and levels of kidney function, they failed to include patients of diverse ancestries. Additionally, current evidence to support DOAC pharmacogenetic associations have primarily been derived from European and Asian individuals. Given differences in genotype frequencies and disease burden among patients of different biogeographic groups, future research must engage diverse populations to assess and quantify the impact of predictors on DOAC response. Current under-representation of patients from diverse racial groups does not allow for proper generalization of the influence of clinical and genetic factors in relation to DOAC variability. Herein, we discuss factors affecting DOAC response, such as age, sex, weight, kidney function, drug interactions, and pharmacogenetics, while offering a new perspective on the need for further research including frequently excluded groups.

中文翻译：

---

针对不同人群的个性化直接口服抗凝治疗：种族、肾功能、药物相互作用和药物遗传学的作用


口服抗凝剂（OAC）通常用于降低房颤患者静脉血栓栓塞的风险和中风的风险。经美国心脏协会、美国心脏病学会和欧洲心脏病学会认可，直接口服抗凝剂 (DOAC) 已取代华法林，成为治疗这两种疾病的首选 OAC，原因是安全性提高、药物间和药物间减少。饮食相互作用，以及缺乏监测要求。尽管 DOAC 被广泛使用且安全性优于华法林，但 DOAC 相关的出血仍然是患者的主要担忧。 DOACs具有稳定的药代动力学和药效学；然而，DOAC 反应的变异性很常见，可能归因于多种因素，包括患者特异性因素、伴随药物、合并症和遗传学。尽管 DOAC 随机对照试验纳入了不同年龄和肾功能水平的患者，但未能纳入不同血统的患者。此外，目前支持 DOAC 药物遗传学协会的证据主要来自欧洲和亚洲个体。鉴于不同生物地理群体的患者之间基因型频率和疾病负担的差异，未来的研究必须让不同的人群参与来评估和量化预测因素对 DOAC 反应的影响。目前来自不同种族群体的患者代表性不足，无法正确概括与 DOAC 变异相关的临床和遗传因素的影响。 在此，我们讨论了影响 DOAC 反应的因素，例如年龄、性别、体重、肾功能、药物相互作用和药物遗传学，同时就包括经常被排除的群体在内的进一步研究的必要性提供了新的视角。