直接凝血酶抑制剂。
Direct thrombin inhibitors.
机构信息
Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, USA.
出版信息
Br J Clin Pharmacol. 2011 Oct;72(4):581-92. doi: 10.1111/j.1365-2125.2011.03916.x.
Abstract
Heparins and vitamin K antagonists have been the primary agents used for anticoagulation in certain cardiovascular and thromboembolic diseases for over 50 years. However, they can be difficult to administer and are fraught with limitations. In response to the need for new anticoagulants, direct thrombin inhibitors (DTIs) have been developed and investigated for their utility in prophylaxis and treatment of venous thromboembolism (VTE), heparin-induced thrombocytopenia (HIT), acute coronary syndromes (ACS), secondary prevention of coronary events after ACS, and nonvalvular atrial fibrillation. Currently, four parenteral direct inhibitors of thrombin activity are FDA-approved in North America: lepirudin, desirudin, bivalirudin and argatroban. Of the new oral DTIs, dabigatran etexilate is the most studied and promising of these agents. This review discusses the clinical indications and efficacy of these direct thrombin inhibitors as well as future directions in anticoagulant therapy.
摘要
肝素和维生素 K 拮抗剂在过去 50 多年中一直是某些心血管和血栓栓塞性疾病中抗凝的主要药物。然而，它们的给药较为困难，并且存在许多限制。为了满足对新型抗凝剂的需求，已经开发并研究了直接凝血酶抑制剂（DTIs），以将其用于预防和治疗静脉血栓栓塞症（VTE）、肝素诱导的血小板减少症（HIT）、急性冠状动脉综合征（ACS）、ACS 后冠状动脉事件的二级预防和非瓣膜性心房颤动。目前，有四种肠外直接凝血酶活性抑制剂获得了北美 FDA 的批准：来匹卢定、地西卢定、比伐卢定和阿加曲班。在新型口服 DTIs 中，达比加群酯是研究最多且最有前途的药物。本文综述了这些直接凝血酶抑制剂的临床适应证和疗效，以及抗凝治疗的未来方向。
相似文献
1
Direct thrombin inhibitors.直接凝血酶抑制剂。
Br J Clin Pharmacol. 2011 Oct;72(4):581-92. doi: 10.1111/j.1365-2125.2011.03916.x.
2
[Direct inhibitors of thrombin, hirudin, bivalirudin, and dabigatran etexilate].[凝血酶直接抑制剂、水蛭素、比伐卢定和达比加群酯]
J Mal Vasc. 2011 Feb;36(1):24-32. doi: 10.1016/j.jmv.2010.11.005. Epub 2011 Jan 15.
3
Direct thrombin and factor Xa inhibitors in children: a quest for new anticoagulants for children.儿童直接凝血酶抑制剂和Xa因子抑制剂：寻找新型儿童抗凝剂
Wien Med Wochenschr. 2011 Feb;161(3-4):73-9. doi: 10.1007/s10354-011-0879-5.
4
Dabigatran etexilate: an oral direct thrombin inhibitor for prophylaxis and treatment of thromboembolic diseases.达比加群酯：一种用于预防和治疗血栓栓塞性疾病的口服直接凝血酶抑制剂。
Pharmacotherapy. 2008 Nov;28(11):1354-73. doi: 10.1592/phco.28.11.1354.
5
[New anticoagulants - direct thrombin inhibitors].[新型抗凝剂——直接凝血酶抑制剂]
Ther Umsch. 2012 Nov;69(11):643-9. doi: 10.1024/0040-5930/a000342.
6
New anticoagulant agents: direct thrombin inhibitors.新型抗凝剂：直接凝血酶抑制剂
Cardiol Clin. 2008 May;26(2):169-87, v-vi. doi: 10.1016/j.ccl.2007.12.005.
7
New developments in parenteral anticoagulation for arterial and venous thromboembolism.静脉和动脉血栓栓塞症的肠外抗凝新进展。
Best Pract Res Clin Haematol. 2013 Jun;26(2):203-13. doi: 10.1016/j.beha.2013.07.010. Epub 2013 Jul 21.
8
Direct thrombin inhibitors fail to reverse the negative effects of heparin on lung growth and function after murine left pneumonectomy.直接凝血酶抑制剂无法逆转肝素对小鼠左肺切除术后肺生长和功能的负面影响。
Am J Physiol Lung Cell Mol Physiol. 2024 Mar 1;326(3):L213-L225. doi: 10.1152/ajplung.00096.2023. Epub 2023 Dec 19.
9
Anticoagulation for acute coronary syndromes: from heparin to direct thrombin inhibitors.急性冠状动脉综合征的抗凝治疗：从肝素到直接凝血酶抑制剂
Rev Cardiovasc Med. 2007;8 Suppl 3:S9-17.
10
Dabigatran etexilate: A novel oral direct thrombin inhibitor.达比加群酯：一种新型口服直接凝血酶抑制剂。
Am J Health Syst Pharm. 2011 Aug 15;68(16):1506-19. doi: 10.2146/ajhp100348.
引用本文的文献
1
Direct thrombin inhibition during pulmonary vein isolation using pulsed field ablation.在使用脉冲场消融进行肺静脉隔离期间直接抑制凝血酶
HeartRhythm Case Rep. 2025 May 8;11(7):671-674. doi: 10.1016/j.hrcr.2025.04.020. eCollection 2025 Jul.
2
Evaluation of a Bivalirudin Dosing and Monitoring Protocol in Pediatric Extracorporeal Membrane Oxygenation.小儿体外膜肺氧合中比伐卢定给药与监测方案的评估
J Pediatr Pharmacol Ther. 2025 Apr;30(2):218-225. doi: 10.5863/1551-6776-30.2.218. Epub 2025 Apr 14.
3
Delineation of a thrombin receptor-stimulated vascular smooth muscle cell transition generating cells in the plaque-stabilising fibrous cap.确定凝血酶受体刺激的血管平滑肌细胞转变产生斑块稳定纤维帽中的细胞。
Cardiovasc Res. 2025 Jun 27. doi: 10.1093/cvr/cvaf112.
4
Evolving anticoagulation paradigms in left ventricular assist device (LVAD) patients: a focus on direct oral anticoagulants.左心室辅助装置（LVAD）患者不断演变的抗凝模式：聚焦直接口服抗凝剂。
Heart Fail Rev. 2025 Jun 17. doi: 10.1007/s10741-025-10537-8.
5
Drug repurposing of argatroban, glimepiride and ranolazine shows anti-SARS-CoV-2 activity via diverse mechanisms.阿加曲班、格列美脲和雷诺嗪的药物重新利用通过多种机制显示出抗SARS-CoV-2活性。
Heliyon. 2025 Jan 10;11(3):e41894. doi: 10.1016/j.heliyon.2025.e41894. eCollection 2025 Feb 15.
6
Venom-derived peptides for breaking through the glass ceiling of drug development.用于突破药物研发瓶颈的毒液衍生肽。
Front Chem. 2024 Sep 26;12:1465459. doi: 10.3389/fchem.2024.1465459. eCollection 2024.
7
A safety comparison of heparin and argatroban anticoagulation in veno-venous extracorporeal membrane oxygenation with a focus on bleeding.肝素与阿加曲班在静脉-静脉体外膜肺氧合中抗凝作用的安全性比较，重点关注出血情况。
Transfus Med. 2025 Feb;35(1):75-81. doi: 10.1111/tme.13102. Epub 2024 Oct 7.
8
Comparative Cardioprotective Effectiveness: NOACs vs. Nattokinase-Bridging Basic Research to Clinical Findings.比较心脏保护效果：NOACs 与纳豆激酶-将基础研究与临床发现联系起来。
Biomolecules. 2024 Aug 7;14(8):956. doi: 10.3390/biom14080956.
9
Chemical Synthesis and Structure-Activity Relationship Studies of the Coagulation Factor Xa Inhibitor Tick Anticoagulant Peptide from the Hematophagous Parasite .吸血寄生虫凝血因子Xa抑制剂蜱抗凝肽的化学合成及构效关系研究
Biomimetics (Basel). 2024 Aug 12;9(8):485. doi: 10.3390/biomimetics9080485.
10
Rational Design of Selective TMPRSS6 Peptidomimetic Inhibitors via Exploitation of the S2 Subpocket.通过利用 S2 亚口袋合理设计选择性 TMPRSS6 肽模拟物抑制剂。
J Med Chem. 2024 Aug 8;67(15):12969-12983. doi: 10.1021/acs.jmedchem.4c00922. Epub 2024 Jul 19.
本文引用的文献
1
Effectiveness of dabigatran etexilate for thromboprophylaxis of mechanical heart valves.达比加群酯预防机械心脏瓣膜血栓形成的疗效。
J Thorac Cardiovasc Surg. 2011 Jun;141(6):1410-6. doi: 10.1016/j.jtcvs.2011.02.011. Epub 2011 Mar 22.
2
Newly identified events in the RE-LY trial.RE-LY试验中的新发现事件。
N Engl J Med. 2010 Nov 4;363(19):1875-6. doi: 10.1056/NEJMc1007378.
3
In vitro comparison of dabigatran, unfractionated heparin, and low-molecular-weight heparin in preventing thrombus formation on mechanical heart valves.在体比较达比加群、未分级肝素和低分子肝素预防机械心脏瓣膜血栓形成的效果。
Thromb Res. 2010 Sep;126(3):e196-200. doi: 10.1016/j.thromres.2010.06.011. Epub 2010 Jul 24.
4
Oral IIa inhibitors.口服 IIa 抑制剂。
Hematol Oncol Clin North Am. 2010 Aug;24(4):739-53, ix. doi: 10.1016/j.hoc.2010.05.001.
5
Drug and dietary interactions of the new and emerging oral anticoagulants.新型和新兴口服抗凝药物的药物和饮食相互作用。
Int J Clin Pract. 2010 Jun;64(7):956-67. doi: 10.1111/j.1742-1241.2009.02286.x.
6
Rationale and design of the PREVENT-HIT study: a randomized, open-label pilot study to compare desirudin and argatroban in patients with suspected heparin-induced thrombocytopenia with or without thrombosis.预防-HIT 研究的原理和设计：一项比较依诺肝素和阿加曲班在疑似肝素诱导的血小板减少症伴或不伴血栓形成患者中的随机、开放标签的初步研究。
Clin Ther. 2010 Apr;32(4):626-36. doi: 10.1016/j.clinthera.2010.04.012.
7
Dabigatran etexilate--a novel, reversible, oral direct thrombin inhibitor: interpretation of coagulation assays and reversal of anticoagulant activity.达比加群酯——一种新型、可逆、口服直接凝血酶抑制剂：凝血检测的解读及其抗凝活性的逆转。
Thromb Haemost. 2010 Jun;103(6):1116-27. doi: 10.1160/TH09-11-0758. Epub 2010 Mar 29.
8
Safety and tolerability of an immediate-release formulation of theoral direct thrombin inhibitor AZD0837 in the prevention of stroke and systemic embolism in patients with atrial fibrillation.直接口服抗凝剂 AZD0837 速释制剂预防房颤患者卒中及全身性栓塞的安全性和耐受性。
Thromb Haemost. 2010 Mar;103(3):604-12. doi: 10.1160/TH09-07-0509. Epub 2010 Jan 13.
9
Drug-induced liver injury in humans: the case of ximelagatran.人类药物性肝损伤：希美加群的案例
Handb Exp Pharmacol. 2010(196):407-18. doi: 10.1007/978-3-642-00663-0_13.
10
Dabigatran versus warfarin in the treatment of acute venous thromboembolism.达比加群酯与华法林治疗急性静脉血栓栓塞症的比较。
N Engl J Med. 2009 Dec 10;361(24):2342-52. doi: 10.1056/NEJMoa0906598.
Zotero 插件