Recent developments in antithrombotic therapy: will sodium warfarin be a drug of the past?
Recent developments in antithrombotic therapy: will sodium warfarin be a drug of the past?
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DOI：
10.2174/157489006778777016
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发表时间：
2006-11-01
期刊：
影响因子：
--
通讯作者：
Geha, Alexander S
中科院分区：
文献类型：
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作者：
Desai, Sapan S;Massad, Malek G;Geha, Alexander S
华法林和肝素已成为预防深静脉血栓形成（DVT）、预防房颤卒中和治疗血栓栓塞性疾病（TED）的主要药物。然而，这些选择受到难以给药、与其他药物相互作用、副作用特征和有限的治疗适应症的阻碍。抗Xa因子（抗Xa）抑制剂已经进入药物市场，药物磺达肝素是美国食品和药物管理局（FDA）批准使用的第一种抗Xa抑制剂，其他药物如idraparinux目前正在开发中。一类新的药物，称为直接凝血酶抑制剂（DTI），包括已被FDA批准的母体药物来匹卢定、阿加曲班和比伐卢定，以及口服药物昔美拉唑、美拉唑和达比加群。后三种口服药物可能很快取代华法林和肝素，成为预防DVT和降低卒中相对风险的首选药物。这些药物不依赖于阻断丝氨酸蛋白酶，也不需要辅助因子（抗凝血酶III），如普通肝素（UFH）或低分子量肝素（LMWH）。DTI起效迅速，易于给药，不与其他药物或食物相互作用，副作用有限，并且可以以固定剂量给药。DTI ximelaglavin已经在几个欧洲和亚洲国家获得批准，并且已经进行了十几项随机临床试验，证明其性能与华法林相当。然而，鉴于目前正在评估的肝酶升高的报告发生率，FDA在美国的批准仍悬而未决。本文综述了DTI在预防和治疗TED中的作用以及文献中报道的最新专利。
Warfarin and heparin have formed the mainstay in the prophylaxis of deep vein thrombosis (DVT), stroke prevention in atrial fibrillation, and treatment of thromboembolic disease (TED). However, these choices are hampered by difficult administration, interactions with other medications, side effect profile, and limited indications for treatment. Anti-factor Xa (anti-Xa) inhibitors have already entered the drug market with the drug Fondaparinux being the first anti-Xa inhibitor to be approved for use in the U.S. by the Food and Drug Administration (FDA), and other drugs such as idraparinux being currently in development. A new class of medications, known as direct thrombin inhibitors (DTI), includes the parental agents lepirudin, argatroban and bivalirudin which have been approved by the FDA and the oral agents ximelagatran, melagatran and dabigatran. The latter three drugs which are oral DTIs may soon replace warfarin and heparin as the preferred medications for DVT prophylaxis and for reducing the relative risk of stroke. These drugs do not rely on blocking serine proteases nor do they require a co-factor (antithrombin III) like unfractionated heparin (UFH) or low molecular weight heparin (LMWH). DTIs are rapid in onset, easy to administer, do not interact with other medications or foods, have limited side effects, and can be administered in a fixed dose. The DTI ximelagatran has already been approved in several European and Asian countries, and over a dozen randomized clinical trials have been conducted demonstrating its performance to be on par with warfarin. However, approval by the FDA in the U.S. remains pending in view of reported incidences of elevations in hepatic enzymes that are currently under evaluation. This review examines the role of DTIs in the prevention and treatment of TED and the recent patents reported in the literature.