Estimated Theoretical Benefit of Aggressive LDL Lowering in Patients With Symptomatic Intracranial Atherosclerosis.

IF 7.7 1区 医学 Q1 CLINICAL NEUROLOGY
Neurology Pub Date : 2025-07-08 Epub Date: 2025-05-30 DOI:10.1212/WNL.0000000000213768
James Ernest Siegler, Elena Badillo Goicoechea, Shadi Yaghi, Rami Z Morsi, Andrea Arevalo, Matthew M Smith, Sachin Kothari, Harsh Desai, Neha Sehgal, Rohini Rana, Caroline Alice Kellogg, Aditya Jhaveri, Adam de Havenon, Therese Dunne, Kamil Cameron, Seemant Chaturvedi, Malik Ghannam, Shyam Prabhakaran, Elisheva Coleman, James R Brorson, Rachel Mehendale, Tareq Kass-Hout
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引用次数: 0

Abstract

Objectives: Given the high risk of recurrent atherosclerotic vascular events in patients with stroke due to intracranial atherosclerotic disease (ICAD), we estimated the potential benefit of proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) in this population.

Methods: In this secondary analysis of the Stenting and Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis (SAMMPRIS) trial, we estimated the association between 30-day low-density lipoprotein (LDL) reduction and recurrent stroke or myocardial infarction (MI) beyond 30 days (primary outcome). Estimates were assessed using adjusted Cox proportional hazards regression. We applied relative LDL reduction estimates from PCSK9i trials to project adjusted incidence rate differences of the primary outcome with an equivalent LDL reduction.

Results: Of the 451 patients from SAMMPRIS, 378 met inclusion criteria. In adjusted Cox regression, every 10 mg/dL LDL improvement was associated with a 9% lower rate of the primary outcome (adjusted hazard ratio 0.91, 95% CI 0.83-0.997). Assuming an average projected effect of PCSK9i, estimating if half of SAMMPRIS patients were treated, PCSK9i use could reduce the annualized risk of the primary outcome by 33.2% in this trial population.

Discussion: Every 10 mg/dL reduction in LDL for patients with stroke due to ICAD is associated with lower rates of recurrent stroke or MI, and this theoretical framework suggests that PCSK9i can help achieve this goal.

Trial registration information: Secondary analysis of NCT00576693 prospectively registered interventional clinical trial. First registered December 7, 2007. Actual study start date: October 2008. https://clinicaltrials.gov/show/NCT00576693.

Classification of evidence: This study provides Class IV evidence that a higher absolute reduction in LDL was associated with a lower risk of recurrent cerebral infarction or MI in patients with recent stroke due to intracranial stenosis.

有症状的颅内动脉粥样硬化患者积极降低LDL的估计理论获益。
考虑到颅内动脉粥样硬化性疾病(ICAD)引起的卒中患者动脉粥样硬化性血管事件复发的高风险,我们估计了蛋白转化酶枯草杆菌素/克辛蛋白9型抑制剂(PCSK9i)在这一人群中的潜在益处。方法:在对支架植入和积极医疗管理预防颅内狭窄患者卒中复发(SAMMPRIS)试验的二次分析中,我们估计了30天低密度脂蛋白(LDL)降低与30天以上卒中复发或心肌梗死(MI)之间的关系(主要结局)。使用调整后的Cox比例风险回归评估估计值。我们应用PCSK9i试验的相对低密度脂蛋白降低估计值来预测具有等效低密度脂蛋白降低的主要结局的调整发生率差异。结果:在SAMMPRIS的451例患者中,378例符合纳入标准。在校正Cox回归中,每10 mg/dL LDL改善与主要结局降低9%相关(校正风险比0.91,95% CI 0.83-0.997)。假设PCSK9i的平均预期效果,估计如果一半的SAMMPRIS患者接受治疗,在该试验人群中使用PCSK9i可以将主要结局的年化风险降低33.2%。讨论:ICAD导致的卒中患者LDL每降低10mg /dL,卒中复发或心肌梗死的发生率就会降低,这一理论框架表明PCSK9i可以帮助实现这一目标。试验注册信息:NCT00576693前瞻性注册干预性临床试验的二次分析。首次注册于2007年12月7日。实际研究开始日期:2008年10月。https://clinicaltrials.gov/show/NCT00576693.Classification证据:该研究提供了IV级证据,表明LDL的绝对降低与近期因颅内狭窄引起的卒中患者复发性脑梗死或MI的风险降低相关。
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来源期刊
Neurology
Neurology 医学-临床神经学
CiteScore
12.20
自引率
4.00%
发文量
1973
审稿时长
2-3 weeks
期刊介绍: Neurology, the official journal of the American Academy of Neurology, aspires to be the premier peer-reviewed journal for clinical neurology research. Its mission is to publish exceptional peer-reviewed original research articles, editorials, and reviews to improve patient care, education, clinical research, and professionalism in neurology. As the leading clinical neurology journal worldwide, Neurology targets physicians specializing in nervous system diseases and conditions. It aims to advance the field by presenting new basic and clinical research that influences neurological practice. The journal is a leading source of cutting-edge, peer-reviewed information for the neurology community worldwide. Editorial content includes Research, Clinical/Scientific Notes, Views, Historical Neurology, NeuroImages, Humanities, Letters, and position papers from the American Academy of Neurology. The online version is considered the definitive version, encompassing all available content. Neurology is indexed in prestigious databases such as MEDLINE/PubMed, Embase, Scopus, Biological Abstracts®, PsycINFO®, Current Contents®, Web of Science®, CrossRef, and Google Scholar.
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