AtRial Cardiopathy and Antithrombotic Drugs In prevention After cryptogenicstroke (ARCADIA)

在三分之一的中风中，无法确定确切的原因。这项提议是为了进行临床试验。 涉及原因不明的中风患者，他们也有房性心脏病，或心脏功能异常改变 心脏的心房组织。其目标是比较两种不同的血液稀释疗法，以确定哪种疗法 最好的预防中风复发。在流行的临床模式下，人们认为心房颤动-a 常见的心律失常-在心脏的左心房形成血栓是必需的，从那里它们 会对脑部造成栓塞并导致中风。因此，除非房颤是明显的，否则患者不会。 接受最能预防栓塞性中风的血液稀释药物。然而，最近的研究表明， 当心房组织和功能有异常改变时，可从左心房进行栓塞 甚至在出现房颤之前。这些异常变化--一种被称为心房性心脏病的情况-- 可能可以解释目前不明原因的许多中风。由于血液稀释治疗使用一种 阿皮沙班等抗凝药已被证明比标准阿司匹林疗法更有效 房颤和房性心脏病之间的相似之处表明，预防心房颤动导致的中风 阿匹沙班在预防房性心脏病患者卒中方面也可能比阿司匹林更有效 也没有房颤。这项应用适用于多中心、生物标记物驱动、随机、双盲、 阿匹沙班与阿司匹林在有房颤证据的患者中的主动对照3期临床试验 心脏病和最近一次原因不明的中风，按现行标准。房性心脏病将被定义为 或更多下列生物标志物：心电图P波终末压力V1和GT导联；5,000微伏*毫秒，左侧 超声心动图心房大小指数≥3.0 cm/m2，血清氨基端B型利钠肽原 Pg/m L。标准的心率监测将在入选前进行，以彻底排除 可能是房颤患者。1100名患者将在2.5年内被招募到120名 NINDS StrokeNet财团中的网站。患者将接受至少1.5年和最长时间的随访 复发性卒中的主要疗效和主要不良事件的主要安全结局 出血和颅内出血。具体目标1将检验阿匹沙班优于 阿司匹林预防心房性心脏病患者再发卒中。对这一假设的验证 通过识别一组新的中风患者，将对预防中风复发产生直接影响 他们从抗凝治疗中受益。特定目标2将检验阿匹沙班的疗效假设 过量的阿司匹林随着房性心脏病的严重程度而增加。对这一假设的验证将有助于确定 房性心脏病是中风的危险因素，并因此为未来的研究奠定了基础 在心房性心脏病患者发生中风之前对其进行治疗。

In one-third of strokes, a definite cause cannot be established. This proposal is for a clinical trial involving patients with a stroke of unknown cause who also have atrial cardiopathy, or abnormal changes in the atrial tissue of the heart. The goal is to compare two different blood-thinning treatments to determine which best prevents recurrent stroke. Under the prevailing clinical paradigm, it is thought that atrial fibrillation—a common disorder of heart rhythm—is required for blood clots to form in the heart's left atrium, from where they can embolize to the brain and cause stroke. Therefore, unless atrial fibrillation is apparent, patients do not receive the types of blood-thinning drugs that best prevent embolic stroke. However, recent research indicates that embolization from the left atrium can occur when there are abnormal changes to atrial tissue and function even before there is atrial fibrillation. These abnormal changes—a condition referred to as atrial cardiopathy— may explain many of the strokes that are currently of unknown cause. Since blood-thinning treatment with an anticoagulant drug such as apixaban has already proven more effective than standard aspirin therapy for preventing stroke from atrial fibrillation, the parallels between atrial fibrillation and atrial cardiopathy suggest that apixaban may also be more effective than aspirin for stroke prevention in patients with atrial cardiopathy and no atrial fibrillation. This application is for a multicenter, biomarker-driven, randomized, double-blind, active-control, phase 3 clinical trial of apixaban versus aspirin in patients who have evidence of atrial cardiopathy and a recent stroke of unknown cause by current criteria. Atrial cardiopathy will be defined as one or more of the following biomarkers: P-wave terminal force in electrocardiogram lead V1 >5,000 µV*ms, left atrial size index ≥3.0 cm/m2 on echocardiogram, and serum amino terminal pro-B-type natriuretic peptide >250 pg/mL. Standard heart-rhythm monitoring will be performed before enrollment to exclude as thoroughly as possible those patients with atrial fibrillation. Eleven hundred patients will be recruited over 2.5 years at 120 sites in the NINDS StrokeNet consortium. Patients will be followed for a minimum of 1.5 years and a maximum of 4 years for the primary efficacy outcome of recurrent stroke and the primary safety outcomes of major hemorrhage and intracranial hemorrhage. Specific Aim 1 will test the hypothesis that apixaban is superior to aspirin for the prevention of recurrent stroke in patients with atrial cardiopathy. Validation of this hypothesis would have immediate implications for preventing recurrent stroke by identifying a new group of stroke patients who benefit from anticoagulant therapy. Specific Aim 2 will test the hypothesis that the efficacy of apixaban over aspirin increases with the severity of atrial cardiopathy. Validation of this hypothesis would help establish atrial cardiopathy as a stroke risk factor, and thus set the stage for future studies to determine the benefit of treating patients with atrial cardiopathy before they ever have a stroke in the first place.