Martí-Fàbregas Joan, Mateo José
Cerebrovascular Unit, Department of Neurology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
Cerebrovasc Dis. 2009;27 Suppl 1:111-9. doi: 10.1159/000200448. Epub 2009 Apr 3.
Vitamin K antagonists are the only oral anticoagulants available and are considered as well-established treatment to prevent a first stroke or a recurrent stroke in patients with atrial fibrillation. The difficulties in the routine management of these patients cause an underuse of vitamin K antagonists. For long-term use, there is a need for safer and more effective oral anticoagulants that do not require routine monitoring of coagulation. Recently, new drugs have been developed and there are a number of clinical trials for the primary and secondary prevention of stroke in atrial fibrillation. The new anticoagulants that are being investigated target factor Xa or thrombin. The factor Xa inhibitors include indirect inhibitors such as idraparinux and biotinylated idraparinux that inhibit factor Xa by potentiating antithrombin. Also being investigated are apixaban and rivaroxaban, orally active agents that inhibit factor Xa directly. Direct thrombin inhibitors include ximelagatran and dabigatran etexilate. Although ximelagatran was withdrawn early because of liver toxicity, it provided convincing evidence that new oral anticoagulants have the potential to replace warfarin. However, even if these new drugs prove superior to dose-adjusted warfarin, their benefits must be substantial (retaining high efficacy with added safety and convenience) to offset their increased cost.
维生素K拮抗剂是仅有的口服抗凝剂，被视为预防心房颤动患者首次中风或复发性中风的成熟疗法。这些患者常规管理中的困难导致维生素K拮抗剂使用不足。对于长期使用而言，需要更安全、更有效的口服抗凝剂，且无需常规监测凝血功能。最近，已研发出新药，并且有多项关于心房颤动中风一级和二级预防的临床试验。正在研究的新型抗凝剂作用于Xa因子或凝血酶。Xa因子抑制剂包括间接抑制剂，如依达肝素和生物素化依达肝素，它们通过增强抗凝血酶来抑制Xa因子。正在研究的还有阿哌沙班和利伐沙班，它们是直接抑制Xa因子的口服活性药物。直接凝血酶抑制剂包括希美加群和达比加群酯。尽管希美加群因肝毒性而早期撤市，但它提供了令人信服的证据，表明新型口服抗凝剂有取代华法林的潜力。然而，即使这些新药被证明优于剂量调整后的华法林，其益处也必须足够大（在保持高效的同时增加安全性和便利性），以抵消其增加的成本。
