Pujadas-Mestres L, Escolar G, Arellano-Rodrigo E, Galán A M
Medical Department, Bristol-Myers Squibb, Madrid, Spain.
Drugs Today (Barc). 2013 Jul;49(7):425-36. doi: 10.1358/dot.2013.49.7.1980498.
Conventional anticoagulant therapies can significantly reduce the risk of stroke and related complications in patients with atrial fibrillation (AF). Classic oral anticoagulants based on vitamin K antagonism have shown effectiveness in the prevention of thromboembolic complications in this clinical setting. Unfortunately, vitamin K antagonists that have shown effectiveness in the prevention of thromboembolic complications in patients with nonvalvular AF hold inherent limitations including delayed onset of action, narrow therapeutic index, variability of their response, need for repeated control and numerous interactions with food and other drugs. Since the frequency of stroke related to AF increases with age, guidelines from different scientific societies advise that the risk of bleeding for a patient should be quantified before exposure to anticoagulation and balanced against the risk of stroke with and without anticoagulation. A consequence of assessing this risk/benefit balance is that not all patients with AF at thromboembolic risk receive adequate anticoagulant treatment. Apixaban is a new oral anticoagulant with a direct, specific and reversible inhibitory action on coagulation factor Xa and with demonstrated safety and efficacy in the prophylaxis and treatment of venous thromboembolism in several clinical studies involving thousands of patients subjected to major orthopedic surgery. Results of two large phase III trials have demonstrated the efficacy and safety of apixaban compared with aspirin or warfarin, in the prevention of stroke in patients with AF. Apixaban demonstrated superiority over classic vitamin K antagonists on the previously specified outcomes of stroke, systemic embolism, major bleeding and death. For those patients unsuitable for treatment with vitamin K antagonists because of an excessive bleeding risk, apixaban showed more efficacy than aspirin in stroke prevention with a not statistically significant modest increase of major bleeding.
传统抗凝疗法可显著降低心房颤动(AF)患者中风及相关并发症的风险。基于维生素K拮抗作用的经典口服抗凝剂已在该临床环境中显示出预防血栓栓塞并发症的有效性。不幸的是,在非瓣膜性AF患者中已显示出预防血栓栓塞并发症有效性的维生素K拮抗剂存在固有局限性,包括起效延迟、治疗指数窄、反应变异性大、需要反复监测以及与食物和其他药物有众多相互作用。由于与AF相关的中风发生率随年龄增加,不同科学学会的指南建议,在患者接受抗凝治疗前应量化其出血风险,并与抗凝和不抗凝时的中风风险进行权衡。评估这种风险/获益平衡的一个后果是,并非所有有血栓栓塞风险的AF患者都能得到充分的抗凝治疗。阿哌沙班是一种新型口服抗凝剂,对凝血因子Xa具有直接、特异性和可逆的抑制作用,并且在涉及数千例接受大型骨科手术患者的多项临床研究中已证明其在预防和治疗静脉血栓栓塞方面具有安全性和有效性。两项大型III期试验的结果表明,与阿司匹林或华法林相比,阿哌沙班在预防AF患者中风方面具有有效性和安全性。在中风、全身性栓塞、大出血和死亡等预先指定的结局方面,阿哌沙班显示出优于经典维生素K拮抗剂。对于因出血风险过高而不适用于维生素K拮抗剂治疗的患者,阿哌沙班在预防中风方面比阿司匹林更有效,且大出血虽有适度增加但无统计学显著差异。