Division of Cardiology, Cardiac Electrophysiology Laboratory, Thomas Jefferson University Hospital, Philadelphia, PA, USA.
Postgrad Med. 2012 Nov;124(6):7-16. doi: 10.3810/pgm.2012.11.2608.
There is a high prevalence of atrial fibrillation in the United States, particularly in the elderly population. Patients with atrial fibrillation are at an increased risk of stroke and anticoagulant therapy is recommended. However, many eligible patients are not receiving therapy due to limitations and concerns related to the use of the vitamin K antagonist warfarin, such as slow onset of action, variable drug metabolism, risk of bleeding, and requirement for monitoring. Novel oral anticoagulants (NOACs) have been developed and may be used as an alternative to warfarin. This review article summarizes the current clinical trial data for warfarin compared with the NOACs dabigatran (direct thrombin inhibitor), and rivaroxaban and apixaban (factor Xa inhibitors). Dabigatran (150 mg twice daily) demonstrated superiority in reducing the stroke or systemic embolism rate compared with warfarin (1.53% vs 1.69%; P < 0.001). The risk of major bleeding was similar for dabigatran and warfarin (3.32% per year vs 3.57% per year; P = 0.32). Rivaroxaban (20 mg once daily) demonstrated noninferiority in reducing the stroke or systemic embolism rate compared with warfarin (2.1% vs 2.4%; P < 0.001). There was no significant difference between rivaroxaban and warfarin for the risk of major bleeding and clinically relevant nonmajor bleeding (14.9% per year vs 14.5% per year; P = 0.44). Apixaban (5 mg twice daily) demonstrated superiority compared with warfarin in preventing stroke or systemic embolism (1.27% vs 1.60%; P = 0.01). Apixaban significantly reduced major bleeding compared with warfarin (2.13% per year vs 3.09% per year; P < 0.001). Compared with warfarin, all-cause mortality was numerically lower for dabigatran (P = 0.051) and similar for rivaroxaban (P = 0.15). Apixaban demonstrated significantly lower mortality rates compared with warfarin (3.52% vs 3.94%; P = 0.047). All 3 NOACS--dabigatran, rivaroxaban, and apixaban--significantly reduced intracranial hemorrhage compared with warfarin. Novel oral anticoagulants may be a suitable alternative to warfarin for different patient populations due to minimal drug interactions, lower bleeding risk, and no monitoring requirement.
美国心房颤动的患病率很高，尤其是在老年人群中。心房颤动患者发生中风的风险增加，建议进行抗凝治疗。然而，许多符合条件的患者并未接受治疗，原因是与维生素 K 拮抗剂华法林的使用相关的局限性和担忧，如起效缓慢、药物代谢变异性、出血风险和监测需求。新型口服抗凝剂（NOACs）已被开发出来，可作为华法林的替代药物。本文综述了华法林与新型口服抗凝剂达比加群（直接凝血酶抑制剂）、利伐沙班和阿哌沙班（Xa 因子抑制剂）的临床试验数据。达比加群（150 mg，每日 2 次）在降低中风或全身性栓塞发生率方面优于华法林（1.53%比 1.69%；P<0.001）。达比加群和华法林的大出血风险相似（每年 3.32%比每年 3.57%；P=0.32）。利伐沙班（20 mg，每日 1 次）在降低中风或全身性栓塞发生率方面不劣于华法林（2.1%比 2.4%；P<0.001）。利伐沙班与华法林在大出血和有临床意义的非大出血风险方面无显著差异（每年 14.9%比每年 14.5%；P=0.44）。阿哌沙班（每日 2 次，5 mg）在预防中风或全身性栓塞方面优于华法林（1.27%比 1.60%；P=0.01）。阿哌沙班显著降低了大出血风险，优于华法林（每年 2.13%比每年 3.09%；P<0.001）。与华法林相比，达比加群的全因死亡率略有降低（P=0.051），利伐沙班的死亡率相似（P=0.15）。阿哌沙班的死亡率显著低于华法林（3.52%比 3.94%；P=0.047）。所有 3 种新型口服抗凝剂——达比加群、利伐沙班和阿哌沙班——与华法林相比，均显著降低了颅内出血风险。由于药物相互作用少、出血风险低和无需监测，新型口服抗凝剂可能是华法林治疗不同患者人群的合适替代药物。
