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

• Status: Not yet recruiting
• Trial end date: 2025-12-31
• Target enrollment: 0
• Participant gender: All

Summary

The study protocol is a single-arm, open label pilot study designed to evaluate the impact of PCSK-9 inhibition on coronary blood flow in patients with stable coronary artery disease. Patients with stable coronary artery disease will be recruited from the BWH Cardiovascular Medicine clinic and/or from the BWH Nuclear Cardiology Laboratory. A target sample size of 35 participants will undergo imaging with N-13 ammonia positron emission tomography (PET) and coronary computed tomography angiography (CCTA) before and after 12 months of PCSK-9 inhibition with Evolocumab to assess changes in myocardial blood flow, plaque volume, and vascular endothelial function.

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Brigham and Women's Hospital
• Treatments: Evolocumab

Criteria

Inclusion Criteria:

• Age: ≥ 50 (men) or ≥ 55 (women)

• Low-density lipoprotein cholesterol (LDL-C) > 90 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