Anticoagulation in ICH Survivors for Prevention and Recovery (ASPIRE)

ICH幸存者的抗凝治疗以预防和恢复（ASPIRE）

• 批准号: 10170976
• 负责人: Hooman Kamel
• 金额: $ 50.28万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-06-01 至 2021-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10170976
• 关键词: 2019-nCoV; Acute; Acute Brain Injuries; Address; Admission activity; Affect; Anticoagulant therapy; Anticoagulants; Anticoagulation; Aspirin; Atrial Fibrillation; Blinded; Blood; Brain Injuries; Brain hemorrhage; C-reactive protein; COVID-19; COVID-19 pandemic; Cerebral Infarction; Cerebral hemisphere hemorrhage; Cessation of life; Clinical; Clinical Trials; Collaborations; Communities; Complication; Computer Interface; Critical Care; Critical Illness; Data; Data Set; Decontamination; Detection; Devices; Disease; Double-Blind Method; Electromagnetics; Endothelium; Enrollment; Face; Ferritin; Fibrin fragment D; Foundations; Fright; Functional disorder; Future; General Hospitals; Guidelines; Head; Hemorrhage; Image; Infection; Inflammatory; Infrastructure; Inpatients; Intensive Care Units; Intervention Studies; Intracranial Hemorrhages; Ischemic Stroke; Knowledge; Lead; Link; Liquid substance; Magnetic Resonance Imaging; Massachusetts; Measures; Medical; Mission; Multicenter Studies; National Institute of Neurological Disorders and Stroke; Nature; Neuraxis; Neurologic; Neurological Models; Oral; Outcome; Patient-Focused Outcomes; Patients; Phase; Phenotype; Physiological; Prevention; Prevention therapy; Prevention trial; Preventive Intervention; Protocols documentation; Public Health; Randomized; Randomized Clinical Trials; Recording of previous events; Recovery; Recurrence; Reporting; Research Design; Risk; Risk Factors; Safety; Serological; Severities; Site; Stroke; Stroke prevention; Survivors; Symptoms; Tablet Computer; Testing; Thrombophilia; Thrombosis; United States National Institutes of Health; Ventilator; Work; Writing; antimicrobial; base; body system; brain health; clinical care; clinical practice; clinical risk; cohort; comorbidity; coronavirus disease; cryogenics; disability; epidemiological model; falls; functional outcomes; functional status; heart rhythm; high risk; improved; improved outcome; instrument; mortality; neuroimaging; novel; patient oriented; patient population; portability; predictive modeling; prevent; primary outcome; public health relevance; recruit; secondary endpoint; stroke risk

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.

房颤是最常见的心律紊乱，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，否则房颤会发生。有脑出血史的患者被排除在房颤患者抗凝治疗的临床试验之外。是否在这些患者中使用抗凝是一个主要的知识缺口和临床困境。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，在房颤和近期脑出血患者中，抗凝与缺血性卒中风险降低和总体死亡率相关，而复发出血性卒中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预后相关。尽管这些数据令人信服，但它们是观察性发现，容易混淆和偏差。在临床实践中，约有三分之一的脑出血和房颤患者接受抗凝治疗，其余患者接受抗血小板治疗，如阿司匹林。目前的临床指南要求进行随机、盲法临床试验，以提供高质量的证据来确定最佳治疗方法。阿哌沙班（apixaban）是一种相对较新的口服抗凝药物，在最近的一项头对头试验中发现，阿哌沙班与阿司匹林有相似的出血风险，这使得进行临床试验的理由更加有说服力。本申请是一项多中心、双盲、随机对照阿哌沙班与阿司匹林在房颤合并近期脑出血患者中的临床试验。将在NINDS StrokeNet的125个地点招募700名患者并进行1至3年的随访。该研究的目的是验证阿哌沙班与阿司匹林相比改善预后的假设。主要结局将是任何中风（缺血性或出血性）或死亡。这一综合结果兼顾了疗效和安全性，是卒中预防试验中常用的具有临床意义的终点。次要终点将是功能状态，通过修改的兰金量表评分来衡量。这一次要终点将用于检验阿哌沙班不仅可以减少卒中复发，而且可以减少卒中发生的严重程度的假设。如果得到证实，这一新发现将为初步试验结果提供一个重要的以患者为中心的背景。这一建议提供了一个机会，通过关注他们的大脑健康，在急性环境和长期脑出血患者的预后。这项研究的影响在于，无论其结果的方向如何，它的成功完成将立即指导临床护理，并为心房颤动和其他类型出血患者的抗血栓治疗的未来试验奠定基础。

项目成果

Effect of Intensive Blood Pressure Control on Incident Stroke Risk in Patients With Mild Cognitive Impairment.

• DOI: 10.1161/strokeaha.122.038818
• 发表时间: 2022-07
• 期刊: STROKE
• 影响因子: 8.3
• 作者: de Havenon, Adam;Sharma, Richa;Falcone, Guido J.;Prabhakaran, Shyam;Sheth, Kevin N.
• 通讯作者: Sheth, Kevin N.

Disability Status and Secondary Prevention Among Survivors of Stroke: A Cross-Sectional Analysis of the 2011 to 2018 National Health and Nutrition Examination Survey.

• DOI: 10.1161/jaha.123.030869
• 发表时间: 2023-12-05
• 期刊: Journal of the American Heart Association
• 影响因子: 5.4

Anticoagulation after intracerebral hemorrhage: a perfect clinical scenario for genetics-based precision medicine.

脑出血后抗凝：基于遗传学的精准医学的完美临床方案。

• DOI: 10.2217/pgs-2019-0181
• 发表时间: 2020
• 期刊: Pharmacogenomics
• 影响因子: 2.1
• 作者: Brown,StacyC;Sheth,KevinN;Falcone,GuidoJ
• 通讯作者: Falcone,GuidoJ

Analysis of Clinical Traits Associated With Cardiovascular Health, Genomic Profiles, and Neuroimaging Markers of Brain Health in Adults Without Stroke or Dementia.

• DOI: 10.1001/jamanetworkopen.2022.15328
• 发表时间: 2022-05-02
• 期刊: JAMA NETWORK OPEN
• 影响因子: 13.8
• 作者: Acosta, Julian N.;Both, Cameron P.;Rivier, Cyprien;Szejko, Natalia;Leasure, Audrey C.;Gill, Thomas M.;Payabvash, Seyedmehdi;Sheth, Kevin N.;Falcone, Guido J.
• 通讯作者: Falcone, Guido J.

Effect of Primary Prophylactic Antiseizure Medication for Seizure Prevention Following Intracerebral Hemorrhage in the ERICH Study.

• DOI: 10.1016/j.jstrokecerebrovasdis.2021.106143
• 发表时间: 2022-01
• 期刊: JOURNAL OF STROKE & CEREBROVASCULAR DISEASES
• 影响因子: 2.5
• 作者: Savalia, Krupa;Sekar, Padmini;Moomaw, Charles J.;Koch, Sebastian;Sheth, Kevin N.;Woo, Daniel;Mayson, Douglas
• 通讯作者: Mayson, Douglas