Anticoagulation in ICH Survivors for Prevention and Recovery (ASPIRE)

房颤是最常见的心律失常，它会使缺血性中风的风险增加3-5倍。抗凝治疗已被证明可以预防60%-80%的因心房颤动而发生的缺血性中风。有脑出血病史的患者已被排除在房颤患者的抗凝临床试验之外。是否在这些患者中使用抗凝是一个重大的知识差距和临床困境。许多临床医生担心，抗凝在预防缺血性中风方面已被证实的益处将被出血性中风的增加所抵消。来自多中心研究的初步数据表明，在房颤和最近的脑出血患者中，抗凝与缺血性中风的风险和总死亡率的降低有关，而复发出血性中风的负担没有抵消增加的影响。这些试验数据还表明，抗凝与更好的长期功能结果有关。尽管这些数据令人信服，但它们是观察性发现，容易产生混淆和偏见。在临床实践中，大约三分之一的脑出血和心房颤动患者接受抗凝治疗，其余的接受阿司匹林等抗血小板治疗。目前的临床指南呼吁进行随机、盲目的临床试验，以提供高质量的证据来确定最佳治疗方案。阿皮沙班是一种相对较新的口服抗凝药物，在最近的一次面对面试验中被发现具有与阿司匹林类似的出血风险，这使得进行临床试验的理由变得更加令人信服。这项应用是一项多中心、双盲、随机的临床试验，阿普沙班与阿司匹林在房颤和最近的脑内出血患者中使用。NINDS StrokeNet的125个地点将招募700名患者，并对其进行为期1至3年的跟踪调查。这项研究的目的将是检验阿皮沙班与阿司匹林相比可以改善结果的假设。主要结果将是任何中风(缺血性或出血性)或死亡。这一综合结果兼顾了有效性和安全性，并代表了中风预防试验中经常使用的具有临床意义的终点。次要终点将是功能状态，通过修改的Rankin量表分数来衡量。这个次要终点将被用来检验这样的假设，即阿匹沙班不仅可以减少中风的复发，而且还可以减少确实发生的任何中风的严重程度。如果得到证实，这一新发现将为初步试验结果提供以患者为中心的重要背景。这项提议提供了一个机会，通过关注脑出血患者的急性期和长期的脑健康来改善他们的预后。这项研究的影响是，无论其结果如何，它的成功完成都将立即指导临床护理，并为未来针对房颤和其他类型出血患者的抗血栓治疗试验奠定基础。

Atrial fibrillation, the most common heart-rhythm disorder, increases the risk of ischemic stroke by 3- to 5-fold. Anticoagulant therapy has been proven to prevent 60-80% of ischemic strokes that would otherwise occur from atrial fibrillation. Patients with a history of intracerebral hemorrhage have been excluded from clinical trials of anticoagulation in patients with atrial fibrillation. Whether to use anticoagulation in these patients represents a major knowledge gap and clinical dilemma. Many clinicians fear that the proven benefit of anticoagulation in preventing ischemic stroke will be offset by an increase in hemorrhagic stroke. Preliminary data from multicenter studies indicate that, in patients with atrial fibrillation and recent intracerebral hemorrhage, anticoagulation is associated with a decreased risk of ischemic stroke and overall mortality with no offsetting increase in the burden of recurrent hemorrhagic stroke. These pilot data also suggest that anticoagulation is associated with better long-term functional outcomes. Although these data are compelling, they are observational findings and subject to confounding and bias. In clinical practice, about one-third of patients with intracerebral hemorrhage and atrial fibrillation receive anticoagulation and the remainder receive antiplatelet therapy such as aspirin. Current clinical guidelines call for randomized, blinded clinical trials to provide high-quality evidence to determine the best treatment. The argument for a clinical trial is made more compelling by the advent of apixaban, a relatively new oral anticoagulant drug, which was found to have similar bleeding risks as aspirin in a recent head-to-head trial. This application is for a multicenter, double-blinded, randomized clinical trial of apixaban versus aspirin in patients with atrial fibrillation and a recent intracerebral hemorrhage. Seven hundred patients will be recruited and followed for 1 to 3 years at 125 sites in NINDS StrokeNet. The aim of the study will be to test the hypothesis that apixaban improves outcomes compared to aspirin. The primary outcome will be any stroke (ischemic or hemorrhagic) or death. This composite outcome addresses both efficacy and safety, and represents a clinically meaningful endpoint often used in stroke prevention trials. The secondary endpoint will be functional status, as measured by the modified Rankin Scale score. This secondary endpoint will be used to test the hypothesis that apixaban not only reduces stroke recurrence but also the severity of any strokes that do occur. If confirmed, this novel finding would provide an important patient-centered context for the primary trial results. This proposal offers an opportunity to improve the outcomes of patients with intracerebral hemorrhage by focusing on their brain health both in the acute setting and over the long term. The impact of this study is that its successful completion, regardless of the direction of its results, would immediately guide clinical care and set the stage for future trials of antithrombotic therapy in patients with atrial fibrillation and other types of bleeding.