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 before randomization) defined as one or more of the following:

  1. Abnormal nuclear perfusion imaging

     1. At least moderate ischemia involving \>10% of the LV myocardium or
     2. Global coronary flow reserve (CFR) \<1.8 or
     3. Stress myocardial blood flow (MBF) \<1.8
  2. Abnormal coronary angiography (invasive coronary angiography or coronary computed tomography)

     1. ≥ 50% stenosis in ≥ 2 coronary vessels or
     2. Diffuse atherosclerosis in a 3-vessel distribution
  3. Elevated coronary calcium score

     1. CAC \>100 + \>1 ASCVD risk factor
     2. CAC \>300
* If the patient is on a statin they must be on a stable dose for at least 3 months prior 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-IV for 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.