Evaluating the effects of PCSK-9 inhibition on blood flow in patients with stable coronary disease

The Impact of Pcsk-9 Inhibition on PET Coronary Flow Reserve in Patients at High Cardiovascular Risk (EMPOWER Study)

This study is testing if a new medication can improve blood flow in people with stable coronary artery disease over a year.

Quick facts

• Phase: Phase 4
• Study type: Interventional
• Enrollment: 50 (estimated)
• Ages: 50 Years to 90 Years
• Sex: All
• Sponsor: Brigham and Women's Hospital (Academic / other)
• Drugs / interventions: Evolocumab
• Locations: 1 site (Boston, Massachusetts)
• Trial ID: NCT05152888 on ClinicalTrials.gov

What this trial studies

This pilot study aims to assess the impact of PCSK-9 inhibition using Evolocumab on coronary blood flow in patients with stable coronary artery disease. It is a single-arm, open-label study that will recruit 50 participants who will undergo imaging with PET and coronary computed tomography angiography before and after 12 months of treatment. A parallel control group of 15 stable CAD patients will also be included to compare changes in myocardial blood flow and inflammatory biomarkers. The study seeks to provide insights into how PCSK-9 inhibition may improve cardiovascular outcomes beyond just reducing plaque burden.

Who should consider this trial

Good fit: Ideal candidates are men aged 50 and older or women aged 55 and older with stable coronary artery disease and elevated LDL cholesterol levels.

Not a fit: Patients with a history of myocardial infarction or stroke, or those who have undergone coronary artery bypass grafting within the last three months may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could lead to improved treatment strategies for patients with stable coronary artery disease, potentially enhancing myocardial blood flow and reducing cardiovascular events.

How similar studies have performed: While the specific approach of this study is novel, previous studies have indicated potential benefits of PCSK-9 inhibition in cardiovascular health, suggesting a promising avenue for further exploration.

Eligibility criteria

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.

Where this trial is running

Boston, Massachusetts

• Brigham and Women's Hospital — Boston, Massachusetts, United States (Recruiting)

Study contacts

• Principal investigator: Diana Lopez, MD — Brigham and Women's Hospital
• Study coordinator: Diana Lopez, MD

Conditions Stable Coronary Disease