Journal article
Estimated Theoretical Benefit of Aggressive LDL Lowering in Patients With Symptomatic Intracranial Atherosclerosis
Neurology, Vol.105(1), e213768
07/08/2025
DOI: 10.1212/WNL.0000000000213768
PMID: 40446174
Abstract
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.
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.
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.
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.
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.
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.
Details
- Title: Subtitle
- Estimated Theoretical Benefit of Aggressive LDL Lowering in Patients With Symptomatic Intracranial Atherosclerosis
- Creators
- James Ernest Siegler - University of ChicagoElena Badillo Goicoechea - University of ChicagoShadi Yaghi - Brown UniversityRami Z Morsi - University of ChicagoAndrea Arevalo - University of ChicagoMatthew M Smith - University of ChicagoSachin Kothari - University of ChicagoHarsh Desai - University of ChicagoNeha Sehgal - University of ChicagoRohini Rana - University of ChicagoCaroline Alice Kellogg - Brown UniversityAditya Jhaveri - University of ChicagoAdam de Havenon - Yale UniversityTherese Dunne - Advocate Lutheran General HospitalKamil Cameron - Delaware State UniversitySeemant Chaturvedi - University of Maryland, BaltimoreMalik Ghannam - University of IowaShyam Prabhakaran - University of ChicagoElisheva Coleman - University of ChicagoJames R Brorson - University of ChicagoRachel Mehendale - University of ChicagoTareq Kass-Hout - University of Chicago
- Resource Type
- Journal article
- Publication Details
- Neurology, Vol.105(1), e213768
- DOI
- 10.1212/WNL.0000000000213768
- PMID
- 40446174
- NLM abbreviation
- Neurology
- ISSN
- 1526-632X
- eISSN
- 1526-632X
- Publisher
- LIPPINCOTT WILLIAMS & WILKINS
- Grant note
- National Institute of Neurological Disorders and Stroke
The authors thank the National Institute of Neurological Disorders and Stroke for making these data available for this analysis.
- Language
- English
- Date published
- 07/08/2025
- Academic Unit
- Neurology
- Record Identifier
- 9984825635802771
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