Bauer Kenneth A
VA Boston Healthcare System and Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
J Thromb Thrombolysis. 2006 Feb;21(1):67-72. doi: 10.1007/s11239-006-5579-4.
Traditional anticoagulant drugs, including unfractionated heparin and warfarin, have several limitations. A new strategy for the design of new antithrombotic drugs is based on selective inhibition of a specific coagulation factor. These include direct thrombin inhibitors and factor Xa inhibitors. Two parenteral direct thrombin inhibitors, lepirudin and argatroban, have FDA approval for the management of heparin-induced thrombocytopenia. Ximelagatran, an oral prodrug of the direct thrombin inhibitor melagatran, has shown efficacy in the prevention and treatment of venous thromboembolism as well as stroke prevention in patients with atrial fibrillation. Fondaparinux is a synthetic pentasaccharide, which binds to antithrombin, thereby indirectly selectively inhibiting factor Xa. Fondaparinux has demonstrated its efficacy compared to low-molecular-weight heparin in randomized clinical trials and is FDA approved for the prevention and treatment of venous thromboembolism. A number of oral direct factor Xa inhibitors as well as other oral direct thrombin inhibitors are in clinical development for the prevention and treatment of thrombosis.
传统的抗凝药物,包括普通肝素和华法林,有几个局限性。设计新型抗血栓药物的一种新策略是基于对特定凝血因子的选择性抑制。这些药物包括直接凝血酶抑制剂和Xa因子抑制剂。两种胃肠外直接凝血酶抑制剂,比伐卢定和阿加曲班,已获得美国食品药品监督管理局(FDA)批准用于治疗肝素诱导的血小板减少症。希美加群是直接凝血酶抑制剂美拉加群的口服前体药物,已显示出在预防和治疗静脉血栓栓塞以及预防心房颤动患者中风方面的疗效。磺达肝癸钠是一种合成的五糖,它与抗凝血酶结合,从而间接选择性抑制Xa因子。在随机临床试验中,磺达肝癸钠已证明其与低分子量肝素相比的疗效,并且已获得FDA批准用于预防和治疗静脉血栓栓塞。一些口服直接Xa因子抑制剂以及其他口服直接凝血酶抑制剂正在进行预防和治疗血栓形成的临床开发。