StATins Use in intRacerebral hemorrhage patieNts (SATURN)

关于他汀类药物是否应该用于高危患者，存在知识差距和临床平衡 适用于脑出血(ICH)，特别是脑叶出血患者，他们是脑出血复发的高危人群。 虽然他汀类药物在减少主要不良心脑血管事件(MACCE)方面的好处很好 已经证实，他汀类药物与脑出血发病率的轻微增加有关，特别是在脑叶脑出血 具有载脂蛋白Eε2和/或ε4基因型的患者，以及存在/出现微出血的情况 梯度回波核磁共振。目前还没有前瞻性或随机化的数据来说明持续治疗与非治疗的效果。 脑出血后停用他汀类药物对脑出血复发和MACCE发生率的影响 术语功能或认知结果，或生活质量。我们提出了多中心、务实、前瞻性、 随机、开放标签、III期临床试验和盲目终点评估(探查)对以下患者的研究 大叶性脑出血服用他汀类药物以确定继续或停止这些药物是最好的 策略。我们特别希望评估停用他汀类药物与继续服用他汀类药物对糖尿病风险的影响。 复发性症状性脑出血与MACCE(症状性缺血性卒中，症状性 心肌梗死，新出现症状的动脉闭塞性疾病(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管重建术，以及血管死亡) 在服用他汀类药物的同时出现大叶性脑出血的患者的数月随访。我们还将检查：1)质量 继续服用他汀类药物与停用他汀类药物的患者的生活、功能和认知结果的比较 重复评估EQ-5D生活质量问卷、修正的Rankin量表和电话 在3、6、9、12、18和24个月时进行蒙特利尔认知评估；2)是否存在与不存在 载脂蛋白Eε2和/或ε4基因型改变了他汀类药物对复发脑出血风险的影响(即载脂蛋白E是否 在接受他汀类药物治疗的患者中，可将基因分型作为对脑出血复发风险分层的生物标志物)。 我们假设：1)大叶性脑出血患者停用他汀类药物可能与药物减少有关 脑出血复发的风险；2)大叶脑出血和载脂蛋白Eε2和/或ε4基因携带者 继续服用他汀类药物有复发脑出血的风险；在这类患者中避免服用他汀类药物 这些生物标志物可能有助于降低脑出血复发的风险。 这项在美国国立卫生研究院卒中网进行的拟议研究将回答一个与日常生活相关的重要临床问题 练习一下。这项研究还将提供一个独特的机会，同时处理非物质文化遗产的重要领域 NINDS PRG和StrokeNet确定的研究：1)预防脑出血复发；2)生物标志物 可能会改变中风患者的治疗决定。旨在预防脑出血及其复发的成功研究 将对公共健康和节约成本产生重大影响。

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.