PCSK9 Inhibition in Patients With Symptomatic Intracranial Atherosclerosis

The purpose of this study will be a dataset that lays the foundation for a randomized
controlled trial of PCSK9 inhibition in intracranial atherosclerotic disease (ICAD) patients,
designed to show a reduction in the primary endpoint of ischemic stroke recurrence. Such a
trial would provide evidence for the utility of alirocumab to prevent recurrent stroke in
ICAD. While we are proposing future studies to reduce recurrent ICAD stroke risk, it should
be noted that, in the long term, our research may lead to effective primary ICAD stroke risk
reduction through PCSK9 inhibition in patients at high risk of stroke identified through
asymptomatic stenosis, post-contrast plaque enhancement (PPE) or intraplaque hemorrhage (IPH)
on vwMRI.

Inclusion Criteria:

- Adult patients, ≥ 18 years of age

- Ischemic stroke (≤ 1 month from onset) in one major vascular territory on
diffusion-weighted MRI

- ICAD plaque of a "major intracranial artery," causing >25% and <99% stenosis

- Eligible arteries: vertebral (V4), basilar, PCA (P1, P2), MCA (M1, M2), terminal ICA,
and ACA (A1)

- Able to tolerate high-dose statin (atorvastatin 40-80 mg)

Exclusion Criteria:

- Stroke mechanism other than ICAD, including history of atrial fibrillation,
hypercoagulability, ipsilateral arterial dissection or carotid stenosis >50%, and rare
causes of stroke such as vasculitis or CADASIL

- Bihemispheric stroke or simultaneous stroke in the anterior and posterior circulation

- Positive pregnancy test

- Gadolinium or PCSK9 inhibitor allergy

- Acute or chronic kidney disease with eGFR<30 ml/min/1.73m2

- Pacemaker or other MRI contraindications per American College of Radiology
guidelines33

- Inability to return for 1-year follow-up clinic visit and vwMRI