Schwarb Heike, Tsakiris Dimitrios A
Heike Schwarb, Diagnostic Hematology, University Hospital Basel, CH-4031 Basel, Switzerland.
Dent J (Basel). 2016 Mar 11;4(1):5. doi: 10.3390/dj4010005.
The ideal anticoagulant is oral, has a wide therapeutic range, predictable pharmacokinetics and pharmacodynamics, a rapid onset of action, an available antidote, minimal side effects and minimal interactions with other drugs or food. With the development of the novel direct oral anticoagulants (DOAC), we now have an alternative to the traditional vitamin K antagonists (VKA) for the prevention and treatment of thrombosis. DOACs have limited monitoring requirements and very predictable pharmacokinetic profiles. They were shown to be non-inferior or superior to VKA in the prophylaxis or treatment of thromboembolic events. Particularly in terms of safety they were associated with less major bleeding, including intracranial bleeding, thus providing a superior benefit for the prevention of stroke in patients with atrial fibrillation. Despite these advantages, there are remaining limitations with DOACs: their dependence on renal and hepatic function for clearance and the lack of an approved reversal agent, whereas such antidotes are successively being made available. DOACs do not need regular monitoring to assess the treatment effect but, on the other hand, they interact with other drugs and interfere with functional coagulation assays. From a practical point of view, the properties of oral administration, simple dosing without monitoring, a short half-life allowing for the possibility of uncomplicated switching or bridging, and proven safety overwhelm the disadvantages, making them an attractive option for short- or long-term anticoagulation.
理想的抗凝剂应是口服制剂,治疗窗宽,药代动力学和药效学可预测,起效迅速,有可用的解毒剂,副作用最小,与其他药物或食物的相互作用最小。随着新型直接口服抗凝剂(DOAC)的发展,我们现在有了一种替代传统维生素K拮抗剂(VKA)的药物,用于预防和治疗血栓形成。DOAC的监测要求有限,药代动力学特征非常可预测。在预防或治疗血栓栓塞事件方面,它们已被证明不劣于或优于VKA。特别是在安全性方面,它们与较少的严重出血相关,包括颅内出血,从而为心房颤动患者预防中风提供了更大的益处。尽管有这些优点,但DOAC仍存在局限性:它们依赖于肾脏和肝脏功能进行清除,且缺乏经批准的逆转剂,不过此类解毒剂正在陆续问世。DOAC不需要定期监测来评估治疗效果,但另一方面,它们会与其他药物相互作用并干扰功能性凝血试验。从实际角度来看,口服给药的特性、无需监测的简单给药方式、短半衰期使得可以轻松转换或桥接,以及已证实的安全性,这些优点超过了缺点,使其成为短期或长期抗凝的有吸引力的选择。