Cardiology Division, Veterans Affairs Central California Health Care System, CA, UCSF School of Medecine, San Francisco, USA.
Am J Cardiovasc Drugs. 2011 Aug 1;11(4):265-75. doi: 10.2165/11592410-000000000-00000.
Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia and is an independent risk factor of potentially catastrophic cardioembolic strokes. AF patients are categorized into high-, intermediate-, and low-risk for thromboembolic complications using the CHADS(2) or CHA(2)DS(2)-VASc scoring system. Oral anticoagulation using warfarin has been the standard therapy for stroke prevention in intermediate- to high-risk AF patients. However, warfarin use has been limited by several factors such as narrow therapeutic windows, drug-drug and drug-food interactions, and hemorrhagic complications. Rigorous research evaluated dual antiplatelet therapy of clopidogrel and aspirin (acetylsalicylic acid) as a potential alternative to warfarin in the ACTIVE W trial. Dual antiplatelet therapy of clopidogrel and aspirin was found to be inferior to warfarin in preventing stroke and systemic embolism with increased bleeding risk. Other extensive research has led to the development of new antithrombotic agents. Recently, dabigatran etexilate 150 mg twice daily, a direct thrombin inhibitor, was approved by the US FDA for stroke prevention in patients with non-valvular AF after it was found to be superior to warfarin in preventing thromboembolic events and associated with less bleeding in the RE-LY trial. It was also cost effective when compared with warfarin. Dabigatran can be considered in high-risk AF patients who are unable or unwilling to comply with the frequent laboratory and clinic visits that are required when receiving treatment with warfarin. Factor Xa inhibitors are another class of new anticoagulants that have been developed. Oral rivaroxaban was non-inferior to warfarin in thromboprophylaxis and with similar bleeding in the ROCKET-AF trial (HR 0.88; p = 0.117). Apixaban, another factor Xa inhibitor, was superior to aspirin in reducing stroke and systemic embolism in patients with AF in the AVERROES trial (HR 0.45; p < 0.001). The results of the ARISTOTLE trial, which is evaluating apixaban against warfarin in ∼18 000 patients with AF, are expected to be available later this year. Edoxaban, another oral factor Xa inhibitor, is currently being evaluated against warfarin in the ENGAGE AF-TIMI 48 trial in ∼20 000 patients with AF. With these new developments, there is a necessity for the clinical practitioner to become familiar with these new and upcoming therapies and guidelines. This review provides an overview of the available data regarding the clinical usefulness of these agents.
心房颤动（AF）是最常见的持续性心律失常，也是潜在灾难性心源性脑栓塞的独立危险因素。AF 患者使用 CHADS₂或 CHA₂DS₂-VASc 评分系统进行血栓栓塞并发症的高、中、低危分类。使用华法林进行口服抗凝治疗一直是中高危 AF 患者预防中风的标准疗法。然而，华法林的使用受到多种因素的限制，如治疗窗狭窄、药物相互作用和药物-食物相互作用以及出血并发症。在 ACTIVE W 试验中，严格的研究评估了氯吡格雷和阿司匹林（乙酰水杨酸）双联抗血小板治疗作为华法林的潜在替代疗法。双联抗血小板治疗的氯吡格雷和阿司匹林在预防中风和全身性栓塞方面的效果不如华法林，且出血风险增加。其他广泛的研究导致了新的抗血栓药物的发展。最近，达比加群酯 150mg，每日两次，一种直接凝血酶抑制剂，在美国食品和药物管理局（FDA）批准用于非瓣膜性 AF 患者的中风预防，因为它在预防血栓栓塞事件方面优于华法林，且与 RE-LY 试验中相关的出血较少。与华法林相比，它也具有成本效益。对于不能或不愿意接受华法林治疗时需要进行的频繁实验室和临床检查的高危 AF 患者，可以考虑使用达比加群酯。Xa 因子抑制剂是另一种新开发的抗凝药物。口服利伐沙班在血栓预防方面不劣于华法林，且在 ROCKET-AF 试验中出血情况相似（HR 0.88；p=0.117）。另一种 Xa 因子抑制剂阿哌沙班在 AVERROES 试验中在 AF 患者中降低中风和全身性栓塞的效果优于阿司匹林（HR 0.45；p<0.001）。预计今年晚些时候，评估阿哌沙班与华法林在约 18000 例 AF 患者中的疗效的 ARISTOTLE 试验结果将会公布。另一种口服 Xa 因子抑制剂依度沙班目前正在 ENGAGE AF-TIMI 48 试验中评估其与华法林的疗效，该试验涉及约 20000 例 AF 患者。随着这些新的发展，临床医生有必要熟悉这些新的和即将出现的治疗方法和指南。这篇综述提供了这些药物的临床应用的相关数据概述。
