Principal Investigator: Adam  DeHavenon
Keywords: Stroke , Repatha , Intracranial Atherosclerosis , Vessel Wall Imaging Department: Neurology
IRB Number: 00121763
Specialty: Neurology, Neurology, Neurology
Sub Specialties: Neuromuscular Diseases, Neuroimaging, Stroke
Recruitment Status: Terminated

Contact Information

Ka-Ho Wong
ka-ho.wong@hsc.utah.edu
801-585-7575

Brief Summary

The purpose of this study will be to understand the underlying mechanism by which PCSK9 inhibition reduces the rate of ischemic stroke seen in the pivotal studies that led to its FDA approval for ASCVD such as ischemic stroke. Those trials (FOURIER and ODYSSEY) enrolled almost 50,000 patients and showed that PCSK9 inhibition therapy is safe and effective. We hypothesize that PCSK9 inhibition lowers the rate of stroke by reducing atherosclerotic plaque, which would be particularly beneficial for patients with intracranial atherosclerosis, who have the highest rate of recurrent stroke of any stroke mechanism. 
The goal of the proposed study is to show that inhibition of PCSK9 with the FDA-approved medication Repatha will reduce validated biomarkers of stroke risk (percent atheroma volume and stenosis) in patients with moderate to severe intracranial atherosclerosis. We propose a single arm study of Repatha in 150 patients with a prior history of ischemic stroke and ICAD causing at least 50% stenosis of a major intracranial artery in the Circle of Willis (index artery). 

Inclusion Criteria

·      Adult patients, ≥ 18 years of age
·      History of ischemic stroke, defined as an episode of neurological dysfunction caused by focal cerebral, spinal, or retinal infarction (American Heart Association definition). 
·      Large vessel atherosclerosis of an intracranial artery in the circle of Willis with 50-99% stenosis by WASID criteria (percent stenosis = (1-[diameter stenosis/diameter normal]) x 100%) on MRA, CTA or DSA
*  Eligible arteries: vertebral (V4), basilar, PCA (P1, P2), MCA (M1, M2), tICA, ACA (A1) 
·      Current statin use or documented contraindication to statin
·      Fasting LDL-C ≥ 70 mg/dL or LDL-C ≥ 60 mg/dL if lipoprotein (a) > 30 mg/dL

Exclusion Criteria

·      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 guidelines24
·      Inability to return for 1-year follow-up clinic visit and vwMRI
Positive Pregnancy Test