Turpie Alexander G G, Purdham Daniel, Ciaccia Antonio
McMaster University, Suite 802, 19 Brant Street, Toronto, ON, M5V 2L2, Canada.
Bayer Inc., Mississauga, ON, Canada.
Ther Adv Cardiovasc Dis. 2017 Sep;11(9):243-256. doi: 10.1177/1753944717714921. Epub 2017 Jun 27.
The nonvitamin K antagonist oral anticoagulants (NOACs), also referred to as direct oral anticoagulants (DOACs), dabigatran, apixaban, edoxaban, and rivaroxaban, have emerged as effective alternatives to vitamin K antagonists (VKAs) across several indications, including the prevention of stroke and systemic embolism (SSE) in patients with atrial fibrillation (AF) and the treatment of venous thromboembolism (VTE). Their use in patients with renal impairment is of particular importance, given the prevalence of renal dysfunction in the indicated populations and the impact of renal function on the metabolism of the NOACs. This publication reviews the pharmacokinetic/pharmacodynamic properties of the NOACs and clinical trial results for patients with renal impairment within the AF and VTE indications. Pharmacokinetic/pharmacodynamic data show the NOACs are dependent on renal clearance to varying extents. Relative to VKAs, the efficacy and safety of the NOACs is preserved in patients with moderate renal impairment. The dosing recommendations for patients with renal impairment differ depending on the NOAC, whereby some of the NOACs require dose reductions based solely on renal function, while others require consideration of additional criteria. However, despite these specific dosing recommendations, emerging real-world evidence suggests patients are not being dosed appropriately, indicating a possible knowledge gap. Adherence to recommended dosing algorithms has implications on the optimal efficacy and safety of the NOACs. To this end, renal function should be assessed in patients on a NOAC, as worsening of renal function may warrant change in the dose of a NOAC or change in oral anticoagulant.
非维生素K拮抗剂口服抗凝药（NOACs），也被称为直接口服抗凝药（DOACs），包括达比加群、阿哌沙班、依度沙班和利伐沙班，已成为维生素K拮抗剂（VKAs）在多种适应症上的有效替代药物，包括预防心房颤动（AF）患者的中风和全身性栓塞（SSE）以及治疗静脉血栓栓塞（VTE）。鉴于在适用人群中肾功能不全的患病率以及肾功能对NOACs代谢的影响，它们在肾功能不全患者中的使用尤为重要。本出版物回顾了NOACs的药代动力学/药效学特性以及在AF和VTE适应症范围内肾功能不全患者的临床试验结果。药代动力学/药效学数据表明，NOACs在不同程度上依赖于肾脏清除率。相对于VKAs，中度肾功能不全患者中NOACs的疗效和安全性得以保留。肾功能不全患者的给药建议因NOAC而异，其中一些NOACs仅根据肾功能就需要降低剂量，而其他一些则需要考虑其他标准。然而，尽管有这些具体的给药建议，但新出现的真实世界证据表明患者未得到适当给药，这表明可能存在知识差距。遵循推荐的给药算法对NOACs的最佳疗效和安全性有影响。为此，接受NOAC治疗的患者应评估肾功能，因为肾功能恶化可能需要改变NOAC的剂量或更换口服抗凝药。
