Division of Cardiology, Newark Beth Israel Medical Center, Newark, NJ; Department of Medicine, Mount Sinai School of Medicine, New York, NY, USA.
Am J Med. 2010 Feb;123(2):103-10. doi: 10.1016/j.amjmed.2009.09.001.
Studies have demonstrated the efficacy and safety of unfractionated heparin and low-molecular-weight heparin in the management of patients with acute coronary syndrome. However, a common limitation of unfractionated heparin and low-molecular-weight heparin is that neither can neutralize clot-bound thrombin. To overcome this limitation of the broad heparin-based anticoagulants, novel anticoagulants targeted for both the free and clot-bound forms of thrombin (direct thrombin inhibitors), or other individual components of the coagulation cascade (eg, direct and indirect factor Xa inhibitors), were developed. These targeted anticoagulation agents showed promising results in preclinical testing and have been evaluated in large-scale clinical acute coronary syndrome trials. This review discusses the disconnect between the excellent preclinical findings obtained with these novel, targeted agents and the efficacy and safety data observed in patients with acute coronary syndrome, compared with the broader-range heparin-based anticoagulants.
研究表明，未分级肝素和低分子量肝素在急性冠状动脉综合征患者的治疗中具有疗效和安全性。然而，未分级肝素和低分子量肝素的一个常见局限性是，两者均不能中和与血栓结合的凝血酶。为了克服基于肝素的抗凝剂的这一局限性，开发了针对游离和与血栓结合形式的凝血酶的新型抗凝剂（直接凝血酶抑制剂）或凝血级联的其他单个成分（例如，直接和间接因子 Xa 抑制剂）。这些靶向抗凝剂在临床前测试中显示出有希望的结果，并已在大型临床急性冠状动脉综合征试验中进行了评估。本综述讨论了这些新型靶向药物与基于肝素的更广泛抗凝剂相比，在与急性冠状动脉综合征患者相关的疗效和安全性数据方面，与出色的临床前发现之间的脱节。
