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失常，可使缺血性中风的风险增加3至5倍。抗凝治疗已被证明可以预防60-80%的缺血性中风，否则会发生房颤。有脑出血病史的患者已从房颤患者抗凝治疗的临床试验中排除。是否在这些患者中使用抗凝治疗是一个主要的知识缺口和临床困境。许多临床医生担心，抗凝治疗在预防缺血性卒中方面已证实的益处将被出血性卒中的增加所抵消。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，抗凝治疗与缺血性卒中风险降低和总体死亡率降低相关，而复发性出血性卒中的负担没有抵消性增加。这些初步数据还表明，抗凝治疗与更好的长期功能结局相关。虽然这些数据是令人信服的，但它们是观察性发现，并受到混淆和偏见的影响。在临床实践中，约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。阿哌沙班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其出血风险与阿司匹林相似。本申请是一项比较阿哌沙班与阿司匹林治疗房颤和近期脑出血患者的多中心、双盲、随机临床试验。将在NINDS StrokeNet的125个研究中心招募700名患者并随访1至3年。该研究的目的是检验与阿司匹林相比，阿哌沙班改善结局的假设。主要结局为任何卒中（缺血性或出血性）或死亡。这一复合结局同时解决了疗效和安全性问题，代表了卒中预防试验中经常使用的具有临床意义的终点。次要终点为功能状态，通过改良兰金量表评分进行测量。该次要终点将用于检验以下假设：阿哌沙班不仅可降低卒中复发率，还可降低任何卒中的严重程度。如果得到证实，这一新发现将为主要试验结果提供一个重要的以患者为中心的背景。这项建议提供了一个机会，以改善脑出血患者的结果，重点是他们的大脑健康，无论是在急性环境和长期。这项研究的影响是，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，并为房颤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