Reducing Intracranial atheroSclErosis With Repatha

Reducing Intracranial atheroSclErosis With Repatha

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. The investigators 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.

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 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 guidelines
• Inability to return for 78 week follow-up clinic visit and vwMRI