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。这份提案是关于临床试验的 涉及不明原因中风的患者，他们也有心房性心脏病，或 心房组织我们的目标是比较两种不同的血液稀释治疗，以确定哪一种 最能预防中风复发在流行的临床范式下，认为心房颤动-a 心脏节律的一种常见紊乱--血栓在心脏的左心房形成所必需的， 会栓塞大脑导致中风因此，除非房颤明显，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， 当心房组织和功能发生异常变化时， 甚至在心房纤颤之前。这些不正常的变化-一种被称为心房性心脏病的疾病- 可以解释许多目前原因不明的中风。自从血液稀释治疗， 抗凝药物如阿哌沙班已经被证明比标准阿司匹林治疗更有效， 预防房颤引起的中风，房颤和房性心脏病之间的相似之处表明， 阿哌沙班在预防心房性心脏病患者中风方面也可能比阿司匹林更有效 没有心房纤颤本申请是一项多中心、生物标志物驱动、随机、双盲、 阿哌沙班与阿司匹林在有心房颤动证据的患者中的活性对照、III期临床试验 心脏病和最近的中风，根据目前的标准，原因不明。心房性心脏病将被定义为 以下生物标志物中的一种或多种：心电图导联V1中的P波终末力> 5，000 µV*ms，左侧 超声心动图心房大小指数≥3.0 cm/m2，血清氨基末端B型利钠肽前体>250 pg/mL。入组前将进行标准心律监测，以尽可能彻底地排除， 可能是房颤患者。将在2.5年内招募1100名患者， NINDS StrokeNet联盟的网站。将对患者进行至少1.5年和最长1.5年的随访。 复发性卒中的主要有效性结局和主要安全性结局为4年 出血和颅内出血。具体目标1将检验阿哌沙班上级 阿司匹林用于预防心房性心脏病患者复发性卒中。验证这一假设 通过识别一组新的中风患者， 从抗凝治疗中获益的人具体目标2将检验阿哌沙班的疗效 阿司匹林过量的风险随着心房性心脏病的严重程度而增加。验证这一假设将有助于建立 心房性心脏病作为中风的危险因素，从而为未来的研究奠定了基础，以确定 在心房性心脏病患者中风之前就开始治疗他们。

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.