A Study of Evolocumab on Carotid Artery Atherosclerotic Plaque Morphology Prior to Carotid EndArterectomy
A Study of Evolocumab on Carotid Artery Atherosclerotic Plaque Morphology Prior to Carotid EndArterectomy
This is a multicenter, randomized, open label study with blinded outcome assessment to
 evaluate the impact of additional/intensive LDL-cholesterol reduction with evolocumab on
 carotid artery atherosclerotic plaques in higher risk subjects with severe asymptomatic but
 vulnerable plaques undergoing carotid endarterectomy.
Inclusion Criteria:

 1. Age ≥ 40 years old

 2. Significant (70-99%) carotid artery stenosis on one side, as measured by duplex
 ultrasound or angiogram

 3. Asymptomatic carotid stenosis (no history of ipsilateral stroke or TIA within 180
 days)

 4. Deemed to be fit for carotid endarterectomy

 5. At least one of the following high risk features: (a) prior stroke >6months prior to
 randomization; (b) peripheral artery disease; (c) current smoker; and/or (d) type II
 diabetes

 6. On a moderate to high intensity statin therapy (defined as atorvastatin 40-80mg daily,
 rosuvastatin 20-40mg or simvastatin 40mg daily) unless a lower dose, or another statin
 or non-statin therapy is clinically justified

 Exclusion Criteria:

 1. Contraindications for MRI (pacemaker; neurostimulator; non-removable metal fragments
 in the eye; etc.)

 2. Patients in whom additional lowering of LDL-C with evolocumab is deemed to be
 clinically inappropriate

 3. Currently taking simvastatin >40mg/day

 4. High risk comorbidities such as severe heart failure, severe COPD, severe renal
 disease, known severe hepatic impairment, unstable coronary syndrome, and/or advanced
 dementia

 5. eGFR <30 mL/min/1.73m2

 6. Anatomic contraindications for CEA such as previous neck radiation or radical neck
 surgery; inaccessible lesion above C2 level; tracheostomy; contralateral laryngeal
 nerve paralysis

 7. Current, prior within past year, or known planned use of PCSK9 inhibition treatment

 8. Known intolerance or allergy to evolocumab or other PCSK9 inhibitors

 9. Known latex allergy

 10. Women who are pregnant or breastfeeding

 11. Women of child bearing potential who are unwilling to use proper family planning or
 birth control methods to avoid pregnancy. Women are considered post-menopausal and not
 of childbearing potential after 12 months of natural (spontaneous) amenorrhea or have
 had a surgical procedure such as hysterectomy which makes pregnancy impossible

 12. Inability to comply with protocol-required study visits or procedures, including
 administration of study drug

 13. Severe concomitant disease that is expected to reduce life expectancy to less than 5
 years

 14. Participation in another investigational device or drug study which is likely to
 affect the primary outcome, within 30 days of planned initiation of study drug

 If all eligibility criteria listed above are met, the participant will undergo a
 time-of-flight MR angiogram, where one additional inclusion criteria will be assessed to
 confirm eligibility:

 1. Evidence of IPH on MRI