Anticoagulation in ICH Survivors for Prevention and Recovery (ASPIRE)

房颤，最常见的心律紊乱，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%的缺血性中风 发生于房颤。有脑出血病史的患者已被排除在 房颤患者抗凝治疗的临床试验。在这些情况下是否使用抗凝 患者代表着一个重大的知识鸿沟和临床困境。许多临床医生担心，已证实的 出血性卒中的增加将抵消抗凝预防缺血性卒中的作用。初步 来自多中心研究的数据表明，在患有心房颤动和最近脑内病变的患者中 出血、抗凝与缺血性中风的风险和总死亡率的降低有关 复发性出血性中风的负担没有抵消性增加。这些试点数据还表明， 抗凝与更好的长期功能结果相关。尽管这些数据令人信服， 它们是观察性的发现，容易产生混淆和偏见。在临床实践中，大约三分之一的人 脑出血和房颤患者接受抗凝治疗，其余患者接受抗凝治疗 抗血小板治疗，如阿司匹林。目前的临床指南要求进行随机、盲法临床试验 提供高质量的证据来确定最佳治疗方案。临床试验的论点被提出了更多 阿匹沙班是一种相对较新的口服抗凝药，被发现具有类似的 在最近的一次针锋相对的试验中，出血的风险与阿司匹林一样。此应用程序适用于多中心、双盲、 近期脑内注射阿司匹林与阿司匹林治疗心房颤动的随机临床试验 大出血。将招募700名患者，并在NINDS的125个地点对其进行为期1至3年的跟踪调查 StrokeNet。这项研究的目的将是检验阿匹沙班与阿皮沙班相比可以改善结果的假设 阿司匹林。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 同时解决了有效性和安全性，并代表了一种临床上有意义的终点，经常用于中风 预防试验。次要端点将处于功能状态，由修改后的Rankin标度来衡量 得分。这个次要终点将被用来检验阿匹沙班不仅可以减少中风的假设 复发，以及发生的任何中风的严重性。如果得到证实，这一新发现将提供一种 主要试验结果的重要背景是以患者为中心。这项提议提供了一个改进的机会 脑出血患者急性期关注脑健康的转归 从环境和长期来看。这项研究的影响是，它的成功完成，无论 其结果的方向，将立即指导临床护理，并为未来的抗血栓药物试验奠定基础 治疗房颤和其他类型出血的患者。

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.