Shrestha Shreya, Coy Shannon, Bekelis Kimon
Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States.
Department of Pathology, Brigham and Women`s Hospital, Harvard Medical School, Boston, MA, United States.
Curr Pharm Des. 2017;23(9):1377-1391. doi: 10.2174/1381612822666161221145614.
Despite numerous advances over the last 50 years, stroke continues to be a leading cause of death and disability worldwide. The treatment and prevention of stroke has undergone extensive study, and significant advances in medical management have occurred within the past decade principally with the development of new classes of orally active anticoagulant drugs. Here we review these recent breakthroughs and the varying roles of anticoagulants and antiplatelet agents in the prevention and management of different ischemic stroke subtypes, as well as describe the benefits and ongoing challenges to incorporating the novel oral anticoagulants (NOACs) into clinical management guidelines. Current guidelines recommend (a) administration of the antiplatelet agent aspirin in the acute management of ischemic stroke, (b) antiplatelet therapy - aspirin, clopidogrel, dypiridamole - in the secondary prevention of noncardioembolic (large artery atherosclerosis) ischemic stroke, and (c) anticoagulants - warfarin and the NOACs - in the secondary prevention of cardioembolic (atrial fibrillation related) ischemic stroke. In phase III clinical trials of the NOACs, dabigatran 150mg BID and apixaban 5mg BID were superior to warfarin in the prevention of stroke/systemic embolism while rivaroxaban 20mg QD demonstrated noninferiority. Both dabigatran and rivaroxaban had similar rates of major bleeding as warfarin but apixaban showed significantly reduced incidence of this complication. As application of novel anticoagulant agents increases, with concomitant study in a variety of clinical settings; their promise in reducing the incidence of stroke, as well as that of therapeutic complications related to warfarin, should be further elaborated.
尽管在过去50年里取得了诸多进展，但中风仍是全球范围内导致死亡和残疾的主要原因。中风的治疗和预防已经历了广泛研究，在过去十年中，随着新型口服活性抗凝药物的开发，医学管理取得了重大进展。在此，我们回顾这些近期的突破以及抗凝剂和抗血小板药物在不同缺血性中风亚型的预防和管理中的不同作用，并描述将新型口服抗凝剂（NOACs）纳入临床管理指南的益处和持续面临的挑战。当前指南推荐：（a）在缺血性中风的急性管理中使用抗血小板药物阿司匹林；（b）在非心源性（大动脉粥样硬化）缺血性中风的二级预防中使用抗血小板治疗——阿司匹林、氯吡格雷、双嘧达莫；（c）在心源性（与心房颤动相关）缺血性中风的二级预防中使用抗凝剂——华法林和NOACs。在NOACs的III期临床试验中，达比加群150mg每日两次和阿哌沙班5mg每日两次在预防中风/全身性栓塞方面优于华法林，而利伐沙班20mg每日一次显示出非劣效性。达比加群和利伐沙班的大出血发生率与华法林相似，但阿哌沙班的这一并发症发生率显著降低。随着新型抗凝剂应用的增加，以及在各种临床环境中的伴随研究，它们在降低中风发生率以及与华法林相关的治疗并发症发生率方面的前景应得到进一步阐述。
