StAtins Use in intRacereberal hemorrhage patieNts MRI (SATURN MRI) Ancillary Study

关于他汀类药物是否应用于脑出血（ICH）患者，特别是复发性ICH高风险的脑叶ICH患者，存在知识缺口。尚无关于ICH后继续与停用他汀类药物对ICH复发风险、心血管事件发生率或长期功能或认知结局和生活质量影响的前瞻性或随机数据。SATURN试验（一项在服用他汀类药物的脑叶ICH患者中进行设盲终点评估的多中心、务实、前瞻性、随机、开放标签、III期临床试验）最近在NIH/NINDS StrokeNet中获得资助，以解决上述不确定性。我们提出了一个辅助MRI研究（SATURN MRI），它建立在SATURN的框架。SATURN的受试者将在基线和24个月时接受标准化脑部MRI，以评估脑小血管疾病（CSVD）标志物的存在和负荷及其进展。主要目的是确定与他汀类药物停药相比，继续长期他汀类药物治疗对CSVD新出血性MRI标志物发生率的影响，即研究结束时MRI显示的脑微出血（CMB）和皮质浅表铁质沉着症（cSS）。次要目的是：1）评估基线MRI上CMB和cSS的存在和负荷是否可用作成像标志物，以分层脑叶ICH患者中他汀类药物治疗的风险/获益; 2）评价他汀类药物继续与停药对研究结束MRI上新缺血性MRI标志物（白色高信号和隐性梗死）发生率的影响。这些信息对于补充SATURN结果的解释将是非常宝贵的。它将提供关于他汀类药物对CSVD标志物进展的影响的独特见解，并可能导致MRI成像标志物作为工具的验证，以帮助ICH患者就他汀类药物使用/持续的安全性以及缓解晚年认知和功能下降做出个性化决策。SATURN和SATURN MRI将为同时解决NINDS PRG和StrokeNet确定的ICH研究中的重要领域提供独特的机会：1）预防ICH复发; 2）可能改变卒中患者治疗决策的生物标志物。此外，SATURN MRI的观察结果可能为进一步研究阐明脑叶ICH相关CSVD的发病机制提供新的假设，并最终导致旨在减轻微血管脑损伤进展和随后残疾的新治疗靶点。这些研究具有重要的潜在公共卫生和实践意义。

There is a knowledge gap as to whether statins should be used in patients with intracerebral hemorrhage (ICH), in particular patients with lobar ICH who are at high-risk for recurrent ICH. There are no prospective or randomized data on the effects of continuation vs. discontinuation of statins after ICH regarding the risks of ICH recurrence, incidence of cardiovascular events, or long-term functional or cognitive outcomes and quality of life. The SATURN trial (a multi-center, pragmatic, prospective, randomized, open-label, Phase III clinical trial with blinded end-point assessment in patients with lobar ICH taking statins) was recently funded within the NIH/NINDS StrokeNet to address the above uncertainties. We propose an ancillary MRI study (SATURN MRI) which builds on SATURN’s framework. Participants in SATURN will undergo a standardized brain MRI at baseline and at 24 months in order to assess for the presence and burden of markers of cerebral small vessel disease (CSVD) and their progression. The main objective is to determine the effects of continued long-term statin therapy compared to statin discontinuation on the incidence of new hemorrhagic MRI markers of CSVD, namely cerebral microbleeds (CMBs) and cortical superficial siderosis (cSS) on end-study MRI. Secondary objectives are: 1) to assess whether the presence and burden of CMBs and cSS on baseline MRI can be used as an imaging marker to stratify the risk/benefit of statin therapy in patients with lobar ICH; and 2) to evaluate the effects of statin continuation vs. discontinuation on the incidence of new ischemic MRI markers (white matter hyperintensities and covert infarcts) on end-study MRI. This information will be invaluable to complement the interpretation of SATURN’s results. It will provide unique insights on the effect of statins on progression of markers of CSVD, and could lead to validation of MRI imaging markers as tools to assist with individualized decision-making regarding the safety of statins use/continuation in ICH patients and the mitigation of late life cognitive and functional decline. SATURN and SATURN MRI will 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. Furthermore, observations from SATURN MRI could lead to novel hypotheses for further research elucidating the pathogenesis of CSVD implicated in lobar ICH and ultimately lead to novel therapeutic targets aimed at mitigating the progression of microvascular cerebral injury and ensuing disability. These studies have important potential public health and practice implications.