Departments of Internal Medicine (Section of Vascular Medicine) and Biochemistry, Thrombosis Expertise Center, and CARIM School for Cardiovascular Diseases, Maastricht University Medical Center, Maastricht, The Netherlands; email:
Section of Pharmacology, Catholic University School of Medicine, Rome, Italy.
Annu Rev Pharmacol Toxicol. 2024 Jan 23;64:551-575. doi: 10.1146/annurev-pharmtox-032823-122811. Epub 2023 Sep 27.
Direct oral anticoagulants (DOACs) have largely replaced vitamin K antagonists, mostly warfarin, for the main indications for oral anticoagulation, prevention and treatment of venous thromboembolism, and prevention of embolic stroke in atrial fibrillation. While DOACs offer practical, fixed-dose anticoagulation in many patients, specific restrictions or contraindications may apply. DOACs are not sufficiently effective in high-thrombotic risk conditions such as antiphospholipid syndrome and mechanical heart valves. Patients with cancer-associated thrombosis may benefit from DOACs, but the bleeding risk, particularly in those with gastrointestinal or urogenital tumors, must be carefully weighed. In patients with frailty, excess body weight, and/or moderate-to-severe chronic kidney disease, DOACs must be cautiously administered and may require laboratory monitoring. Reversal agents have been developed and approved for life-threatening bleeding. In addition, the clinical testing of potentially safer anticoagulants such as factor XI(a) inhibitors is important to further optimize anticoagulant therapy in an increasingly elderly and frail population worldwide.
直接口服抗凝剂（DOACs）已在很大程度上取代了维生素 K 拮抗剂，主要是华法林，用于口服抗凝的主要适应证、预防和治疗静脉血栓栓塞以及预防心房颤动中的栓塞性中风。虽然 DOACs 为许多患者提供了实用的、固定剂量的抗凝治疗，但可能存在特定的限制或禁忌证。DOACs 在高血栓形成风险的情况下（如抗磷脂综合征和机械心脏瓣膜）效果不够理想。癌症相关血栓形成的患者可能受益于 DOACs，但必须仔细权衡出血风险，尤其是胃肠道或泌尿生殖系统肿瘤患者。在虚弱、超重和/或中重度慢性肾脏病患者中，必须谨慎使用 DOACs，并且可能需要实验室监测。已经开发并批准了用于危及生命的出血的逆转剂。此外，对潜在更安全的抗凝剂（如因子 XI(a)抑制剂）的临床测试对于在全球范围内日益老龄化和虚弱的人群中进一步优化抗凝治疗非常重要。
