The Impact of Pcsk-9 Inhibition on PET CFR in Patients at High CV Risk

Intervention Group:

Inclusion Criteria:

• Age: ≥ 50 (men) or ≥ 55 (women)

• Low-density lipoprotein cholesterol (LDL-C) ≥ 70 mg/dL

• Stable coronary artery disease (without plan to undergo revascularization beforerandomization) defined as one or more of the following:

1. Abnormal nuclear perfusion imaging

2. At least moderate ischemia involving >10% of the LV myocardium or

3. Global coronary flow reserve (CFR) <1.8 or

4. Stress myocardial blood flow (MBF) <1.8

5. Abnormal coronary angiography (invasive coronary angiography or coronarycomputed tomography)

6. ≥ 50% stenosis in ≥ 2 coronary vessels or

7. Diffuse atherosclerosis in a 3-vessel distribution

8. Elevated coronary calcium score

9. CAC >100 + >1 ASCVD risk factor

10. CAC >300

• If the patient is on a statin they must be on a stable dose for at least 3 monthsprior to enrollment.

Exclusion Criteria:

• History of myocardial infarction or stroke

• CABG < 3 months prior to screening

• Homozygous familial hypercholesterolemia

• History of cardiac transplantation

• LV ejection fraction < 40% or New York Heart Failure Association (NYHA) class III-IVfor angina and/or dyspnea.

• History of infiltrative or hypertrophic cardiomyopathy

• Severe valvular disease

• Uncontrolled or recurrent ventricular tachycardia

• Fasting triglycerides > 500 mg/dL

• GFR ˂ 30 mL/min/1.73 m²

• Current use of a PCSK-9 inhibitor

• Currently pregnant or breastfeeding

• Contraindication to receive vasodilator agent

• Latex allergy

Parallel Control Group:

Patients will be invited to participate in the parallel control group if they meet study criteria, but 1) have a latex allergy and cannot use the Evolocumab autoinjector 2) LDL-C is just below the enrollment criteria (LDL 60-69), or 3) meet study criteria but prefer to not take an injectable medication at this time.