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

关于他汀类药物是否应该用于脑出血（ICH）患者，特别是具有复发性脑出血高风险的大叶性脑出血患者，目前还存在知识空白。关于脑出血后继续使用他汀类药物与停止使用他汀类药物对脑出血复发风险、心血管事件发生率、长期功能或认知结局和生活质量的影响，尚无前瞻性或随机数据。土星试验（一项多中心、务实、前瞻性、随机、开放标签的III期临床试验，对服用他汀类药物的大叶性脑出血患者进行盲法终点评估）最近由NIH/NINDS StrokeNet资助，以解决上述不确定性。我们提出了一个辅助MRI研究（土星MRI），它建立在土星的框架。SATURN的参与者将在基线和24个月时接受标准化的脑MRI检查，以评估脑血管疾病（CSVD）标志物的存在和负担及其进展。主要目的是确定持续长期他汀类药物治疗与停止他汀类药物治疗对CSVD新出血性MRI标记物发生率的影响，即脑微出血（CMBs）和皮质浅表性铁斑变性（cSS）。次要目的是：1)评估基线MRI上CMBs和cSS的存在和负担是否可以作为他汀类药物治疗对大叶性脑出血患者的风险/获益分层的成像标记；2)评估他汀类药物继续与停药对研究结束时MRI新缺血性MRI标志物（白质高信号和隐蔽性梗死）发生率的影响。这些信息对于解释土星的结果将是非常宝贵的。它将为他汀类药物对心血管疾病标志物进展的影响提供独特的见解，并可能导致MRI成像标志物作为工具的验证，以协助对脑出血患者使用/继续使用他汀类药物的安全性进行个性化决策，并减轻晚年认知和功能衰退。土星和土星MRI将提供一个独特的机会，同时解决脑出血研究中由NINDS PRG和StrokeNet确定的重要领域：1)预防脑出血复发；2)可能改变脑卒中患者治疗决策的生物标志物。此外，土星MRI的观察结果可能为进一步研究阐明与脑叶性脑出血有关的CSVD发病机制提供新的假设，并最终导致新的治疗靶点，旨在减轻微血管脑损伤的进展和随后的残疾。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.