新型口服抗凝药物的安全性

Safety of new oral anticoagulants

新型抗凝药物主要包括直接凝血酶抑制剂和Xa因子抑制剂。其中,直接凝血酶抑制剂达比加群酯口服制剂、直接Xa因子抑制剂利伐沙班和阿哌沙班口服制剂已在我国上市;另外一种直接Xa因子抑制剂贝曲沙班口服制剂也正在进行Ⅲ期临床研究;而直接Xa因子抑制剂爱多沙班口服制剂已在日本上市。达比加群酯致颅内出血发生风险低于华法林,但该药可能增加急性冠状动脉综合征患者严重出血和具有临床意义轻度出血的发生率,以及心肌梗死或急性冠状动脉综合征的发生风险。利伐沙班在预防非瓣膜性心房颤动所致脑卒中和栓塞方面优于华法林,预防骨科术后血栓效果优于依诺肝素,大出血事件发生风险与两药相似,而颅内出血发生风险低于华法林。阿哌沙班在降低心房颤动患者脑卒中或全身性栓塞发生率及病死率方面优于华法林,颅内出血发生率低于华法林,大出血发生率与华法林相似或降低;阿哌沙班的安全性与用药剂量相关。爱多沙班的主要不良反应为出血,用于心房颤动患者的有效性及安全性均优于华法林。贝曲沙班用于全膝关节置换术后预防血栓效果与依诺肝素相似,出血发生率低于依诺肝素。

New oral anticoagulants include direct thrombin inhibitor and factor Xa inhibitors. The direct thrombin inhibitor, dabigatran etexilate, and the factor Xa inhibitor, rivaroxaban and apixaban, have been approved in China; another oral agent, factor Xa inhibitor, betrixaban is being evaluated in a phase m clinical trial; meanwhile the direct factor Xa inhibitor, edoxaban has also been approved in Japan. Compared with warfarin, dabigatran etexilate was superior in reducing the risk of intracerebral hemorrage, but it may be associated with increase of major or clinically significant minor bleeding in patients with acute coronary syndromes and risk of acute myocardial infarction or acute coronary events. Rivaroxaban has been found to be superior to warfarin for stroke prevention in nonvalvular atrial fibrillation with significant reduction in the risk of intracerebral hemorrage, superior to enoxaparin in prophylaxis of venous thromboembolism in orthopedic surgery with similar major bleeding risk. Compared with warfarin, apixaban was superior in reducing the risk of stroke, systemic embolism or death and was associated with less intracerebral hemorrage and a similar or lower rate of major bleeding. The safety of apixaban was associated with its dose. Efficacy and safety of edoxaban were superior to warfarin in atrial fibrillation with the adverse drug reactions of bleeding. Betrixaban was as effective as enoxaparin in preventing venous thromboembolism in knee replacement patients, but had a lower risk of bleeding.