StATins Use in intRacerebral hemorrhage patieNts (SATURN)

他汀类药物在脑出血患者中的应用 (SATURN)

• 批准号: 10410577
• 负责人: Magdy H Selim
• 金额: $ 315.04万
• 依托单位: BETH ISRAEL DEACONESS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-01 至 2028-02-29
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10410577
• 关键词: Address; American; Apolipoprotein E; Area; Arterial Occlusive Diseases; Benefits and Risks; Biological Markers; Blinded; Blood Vessels; Brain hemorrhage; Cardiovascular system; Cause of Death; Cerebral hemisphere hemorrhage; Cessation of life; Clinical; Cognitive; Coronary; Cost Savings; Data; Decision Analysis; Equipoise; Event; Family; Genotype; Healthcare; Hemorrhage; Impaired cognition; Incidence; Individual; Ischemic Stroke; Knowledge; Link; Lobar; Magnetic Resonance Imaging; Myocardial Infarction; National Institute of Neurological Disorders and Stroke; Neurologic; Outcome; Patients; Peripheral; Peripheral arterial disease; Pharmaceutical Preparations; Phase III Clinical Trials; Prevention; Procedures; Public Health; Quality of life; Questionnaires; Randomized; Recurrence; Relative Risks; Research; Retina; Risk; Survivors; Telephone; Uncertainty; United States National Institutes of Health; apolipoprotein E-4; cognitive testing; disability; efficacy outcomes; follow-up; functional disability; high risk; improved; open label; patient subsets; prevent; prospective; risk stratification; safety outcomes; stroke patient; welfare

There is a knowledge gap and clinical equipoise as to whether statins should be used in patients at high risk for intracerebral hemorrhage (ICH), in particular patients with lobar ICH who are at high risk for recurrent ICH. While the benefits of statins in reducing major adverse cerebro-cardio-vascular events (MACCE) are well established, statins have been linked to a slight increase in the incidence of ICH, particularly in lobar ICH patients who have Apolipoprotein E ε2 and/or ε4 genotypes, and the presence/number of microbleeds on gradient-echo MRI. There are no prospective or randomized data on the effects of continuation vs. discontinuation of statins after ICH regarding the risks of ICH recurrence and incidence of MACCE, or long- term functional or cognitive outcomes, or quality of life. We propose a multi-center, pragmatic, prospective, randomized, open-label, Phase III clinical trial with blinded end-point assessment (PROBE) in patients with lobar ICH taking statins to determine whether continuation or discontinuation of these drugs is the best strategy. We specifically wish to evaluate the effects of discontinuing vs. continuing statins on the risk of recurrent symptomatic ICH, and the occurrence of MACCE (symptomatic ischemic stroke, symptomatic myocardial infarction, newly symptomatic arterial occlusive disease (peripheral, retinal, or carotid), revascularization procedures for coronary, carotid, or peripheral arterial disease, and vascular death) during 24 months of follow-up in patients presenting with lobar ICH while taking a statin. We will also examine: 1) quality of life, functional, and cognitive outcomes in patients in whom statins are continued vs. discontinued, by repeated assessments of the EQ-5D quality of life questionnaire, modified Rankin Scale, and Telephone Montreal Cognitive Assessment at 3, 6, 9, 12, 18, and 24 months; and 2) whether the presence vs. absence of APOE ε2 and/or ε4 genotypes modifies the effects of statins on the risk of recurrent ICH, (i.e. whether APOE genotype can be used as a biological marker to stratify the risk of ICH recurrence in statins-treated patients). We hypothesize that: 1) discontinuation of statins in patients with lobar ICH is likely associated with reduced risk of ICH recurrence; and 2) patients with lobar ICH and APOE ε2 and/or ε4 genotypes have an increased risk of recurrent ICH with continuation of statins therapy; and that avoiding statins in this subset of patients with these biological markers might be helpful to reduce the risk of ICH recurrence. This proposed study within the NIH StrokeNet will answer an important clinical question relevant to everyday practice. This study will also provide a unique opportunity to simultaneously address important areas in ICH research identified by the NINDS PRG and StrokeNet: 1) prevention of ICH recurrence; and 2) biomarkers that may modify treatment decisions in stroke patients. Successful studies aiming to prevent ICH and its recurrence would have significant public health and cost-saving implications.

关于他汀类药物是否应该用于高危患者，存在知识缺口和临床平衡 用于脑出血（ICH），特别是复发性ICH风险高的脑叶ICH患者。 虽然他汀类药物在减少主要不良心血管事件（MACCE）方面的益处很好， 已经证实，他汀类药物与ICH发生率的轻微增加有关，特别是在脑叶性ICH中 具有载脂蛋白E ε2和/或ε4基因型的患者， 梯度回波核磁共振成像目前尚无关于继续治疗与 ICH后停用他汀类药物的ICH复发风险和MACCE发生率，或长期- 长期功能或认知结果，或生活质量。我们提出一个多中心、务实、前瞻、 一项随机、开放标签、III期临床试验，在以下患者中进行设盲终点评估（PROBE） 服用他汀类药物以确定是否继续或停用这些药物是最好的 战略我们特别希望评估停用与继续使用他汀类药物对以下风险的影响： 复发性症状性ICH和MACCE（症状性缺血性卒中，症状性 心肌梗死、新症状性动脉闭塞性疾病（外周、视网膜或颈动脉）， 冠状动脉、颈动脉或外周动脉疾病的血运重建手术，以及血管性死亡） 对服用他汀类药物时出现脑叶性ICH的患者进行了数月的随访。我们还将审查：1）质量 继续与停用他汀类药物患者的生活、功能和认知结局， EQ-5D生活质量问卷、改良兰金量表和电话的重复评估 3、6、9、12、18和24个月时的蒙特利尔认知评估;以及2）是否存在与不存在 APOE ε2和/或ε4基因型改变了他汀类药物对ICH复发风险的影响（即APOE是否 基因型可用作他汀类药物治疗患者ICH复发风险分层的生物学标志物）。 我们假设：1）脑叶性ICH患者停用他汀类药物可能与降低 脑出血复发的风险; 2）脑叶性脑出血和APOE ε2和/或ε4基因型患者的脑出血复发风险增加， 继续他汀类药物治疗的复发性ICH风险;在这一亚组患者中避免使用他汀类药物， 这些生物学标志物可能有助于降低ICH复发的风险。 NIH StrokeNet内的这项拟议研究将回答与日常生活相关的重要临床问题 实践这项研究还将提供一个独特的机会，同时解决ICH的重要领域 NINDS PRG和StrokeNet确定的研究：1）预防ICH复发; 2） 可能会改变中风患者的治疗决定。旨在预防ICH及其复发的成功研究 将对公共卫生和节约成本产生重大影响。

项目成果

Diagnostic utility of brain MRI in spontaneous intracerebral hemorrhage: A retrospective cohort study and meta-analysis.

脑 MRI 在自发性脑出血中的诊断效用：回顾性队列研究和荟萃分析。

• DOI: 10.1177/23969873231192761
• 发表时间: 2023
• 期刊: European stroke journal
• 影响因子: 6.1
• 作者: Wilson,Mitch;Wang,Jia-Yi;Andreev,Alexander;Katsanos,AristeidisH;Selim,Magdy;Lioutas,Vasileios-Arsenios
• 通讯作者: Lioutas,Vasileios-Arsenios