Gómez-Outes Antonio, Lecumberri Ramón, Pozo Carmen, Rocha Eduardo
Division of Pharmacology and Clinical Drug Evaluation, Spanish Agency for Medicines and Medical Devices (AEMPS), Madrid, Spain.
Curr Vasc Pharmacol. 2009 Jul;7(3):309-29. doi: 10.2174/157016109788340785.
Anticoagulation is recommended for prophylaxis and treatment of venous thromboembolism (VTE) (deep vein thrombosis and pulmonary embolism) and/or arterial thromboembolism. The therapeutic arsenal of anticoagulants available to clinicians is mainly composed by unfractionated heparin (UFH), low-molecular-weight heparin (LMWH), fondaparinux and oral vitamin K antagonists (VKA) (i.e. warfarin and acenocumarol). These anticoagulants are effective, but they require parenteral administration (UFH, LMWH, fondaparinux) and/or frequent anticoagulant monitoring (intravenous UFH, oral VKA). Novel anticoagulants in clinical testing include orally active direct factor II inhibitors [dabigatran etexilate (BIBR 1048), AZD0837)], parenteral direct factor II inhibitors (flovagatran sodium), orally active direct factor X inhibitors [rivaroxaban (BAY 59-7939), apixaban, betrixaban, YM150, DU-176b, LY-517717, GW813893, TAK-442, PD 0348292] and new parenteral FXa inhibitors [idraparinux, idrabiotaparinux (biotinilated idraparinux; SSR 126517), ultra-low-molecular-weight heparins (ULMWH: AVE5026, RO-14)]. These new compounds have the potential to complement heparins and fondaparinux for short-term anticoagulation and/or to replace VKA for long-term anticoagulation in most patients. Dabigatran and rivaroxaban have been the firsts of the new oral anticoagulants to be licensed for the prevention of VTE after hip and knee replacement surgery. In the present review, we discuss the pharmacology of new anticoagulants, the key points necessary for interpreting the results of studies on VTE prophylaxis and treatment, the results of clinical trials testing these new compounds and their potential advantages and drawbacks over existing therapies.
推荐使用抗凝治疗来预防和治疗静脉血栓栓塞症（VTE）（深静脉血栓形成和肺栓塞）和/或动脉血栓栓塞症。临床医生可用的抗凝治疗药物主要包括普通肝素（UFH）、低分子肝素（LMWH）、磺达肝癸钠和口服维生素K拮抗剂（VKA）（即华法林和醋硝香豆素）。这些抗凝剂是有效的，但它们需要胃肠外给药（UFH、LMWH、磺达肝癸钠）和/或频繁进行抗凝监测（静脉注射UFH、口服VKA）。正在进行临床试验的新型抗凝剂包括口服活性直接凝血因子II抑制剂[达比加群酯（BIBR 1048）、AZD0837]、胃肠外直接凝血因子II抑制剂（氟加群钠）、口服活性直接凝血因子X抑制剂[利伐沙班（BAY 59-7939）、阿哌沙班、贝曲沙班、YM150、DU-176b、LY-517717、GW813893、TAK-442、PD 0348292]和新型胃肠外FXa抑制剂[依达肝素、依达比星肝素（生物素化依达肝素；SSR 126517）、超低分子肝素（ULMWH：AVE5026、RO-14）]。这些新化合物有可能补充肝素和磺达肝癸钠用于短期抗凝，和/或在大多数患者中替代VKA用于长期抗凝。达比加群和利伐沙班是首批被批准用于预防髋膝关节置换术后VTE的新型口服抗凝剂。在本综述中，我们讨论新型抗凝剂的药理学、解读VTE预防和治疗研究结果所需的关键点、测试这些新化合物的临床试验结果以及它们相对于现有疗法的潜在优缺点。
