Chan Noel, Hirsh Jack
Department of Medicine, McMaster University, Hamilton, Ontario, Canada.
Expert Rev Cardiovasc Ther. 2023 Jul-Dec;21(12):913-921. doi: 10.1080/14779072.2023.2271388. Epub 2023 Dec 13.
Currently approved direct oral anticoagulants (DOACs) target thrombin or coagulation factor Xa. Administered in fixed doses without routine laboratory monitoring, DOACs have simplified the approach to oral anticoagulation, when previously the choice was limited to vitamin K antagonists (VKAs).
We discuss a) unresolved issues related to optimal use of DOACs and b) new developments including the potential for FXIa inhibitors to be effective and safer anticoagulants.
By simplifying oral anticoagulation, DOACs have facilitated the uptake of anticoagulation. The DOACs are approved for stroke prevention in atrial fibrillation and for the prevention and treatment of venous thromboembolism, and their indications are expanding to include the prevention of atherothrombosis. DOACs have now replaced vitamin K antagonists (VKAs) for most indications, but not all. DOACs are inferior to VKAs for patients with mechanical heart valves, left ventricular assist device, rheumatic atrial fibrillation, and those with antiphospholipid syndrome, and their safety and efficacy are uncertain in some populations (e.g. advanced renal and liver disease). Impediments to use include concerns for bleeding and cost. The newly developed FXIa and FXIIa inhibitors have the potential to be safer than current anticoagulants, but phase 3 trials are needed to confirm their clinical efficacy and safety.
目前获批的直接口服抗凝剂（DOACs）作用于凝血酶或凝血因子Xa。DOACs采用固定剂量给药，无需常规实验室监测，简化了口服抗凝治疗方法，而此前的选择仅限于维生素K拮抗剂（VKAs）。
我们讨论了a）与DOACs最佳使用相关的未解决问题，以及b）新进展，包括FXIa抑制剂成为有效且更安全抗凝剂的可能性。
通过简化口服抗凝治疗，DOACs促进了抗凝治疗的应用。DOACs被批准用于心房颤动的卒中预防以及静脉血栓栓塞的预防和治疗，其适应证正在扩大至包括动脉粥样硬化血栓形成的预防。目前，DOACs已在大多数适应证中取代了维生素K拮抗剂（VKAs），但并非全部。对于机械心脏瓣膜、左心室辅助装置、风湿性心房颤动患者以及抗磷脂综合征患者，DOACs不如VKAs，并且在某些人群（如晚期肾脏和肝脏疾病患者）中其安全性和有效性尚不确定。使用的障碍包括对出血和成本的担忧。新开发的FXIa和FXIIa抑制剂有可能比目前的抗凝剂更安全，但需要3期试验来证实其临床疗效和安全性。
