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

NCT05152888 | Recruiting Phase 4 FDA Drug

• 1 other identifier: 2021P003360
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief 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 50 participants will undergo imaging with N-13 ammonia or Rubidium-82 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, and plaque volume. To help account for physiological changes that may occur in myocardial blood flow and inflammatory biomarkers during the study period, we will also recruit a parallel control group of stable CAD patients who will undergo similar baseline and 12-month imaging and biomarker assessment. We plan to recruit 15 patients in the parallel control group.

Conditions

Stable Coronary Disease

Outcome Measures

Primary Outcomes (2)

• Coronary Flow Reserve

  Change in global coronary flow reserve (CFR) after 12 months of therapy with Evolocumab

  Change (from baseline) in global CFR, as measured by PET imaging at 52 weeks after initiation of Evolocumab therapy.

• Stress Myocardial Blood Flow (MBF)

  Change in stress Myocardial Blood Flow (MBF) after 12 months of therapy with Evolocumab

  Change (from baseline) in stress MBF, as measured by PET imaging at 52 weeks after initiation of Evolocumab therapy.

Secondary Outcomes (1)

• Total Perfusion Deficit (TPD)

  Change (from baseline) in TPD, as measured by PET imaging at 52 weeks after initiation of Evolocumab therapy.

Study Arms (2)

Evolocumab

EXPERIMENTAL

Informed consent will be obtained from study participants willing to participate in EMPOWER. Study participants will then undergo the baseline rest/stress cardiac PET scan along with CCTA. The final PET scan and CCTA will occur at 12 months after the intervention.

Drug: Evolocumab

Control

NO INTERVENTION

Informed consent will be obtained from study participants willing to participate in EMPOWER. Study participants will then undergo the baseline rest/stress cardiac PET scan along with CCTA. The final PET scan and CCTA will occur at 12 months after the baseline.

Interventions

Evolocumab DRUG

Evolocumab is a human monoclonal antibody that inhibits proprotein convertase subtilisin-kexin type 9 (PCSK9). Evolocumab was FDA approved in 2015 for the treatment of hyperlipidemia and subsequently approved in 2017 for the prevention of stroke and heart attack. 140mg single use SureClick autoinjector that is administered subcutaneously once every 2 weeks.

Also known as: Repatha

Evolocumab

Eligibility Criteria

• Age: 50 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• Abnormal nuclear perfusion imaging
• At least moderate ischemia involving \>10% of the LV myocardium or
• Global coronary flow reserve (CFR) \<1.8 or
• Stress myocardial blood flow (MBF) \<1.8
• Abnormal coronary angiography (invasive coronary angiography or coronary computed tomography)
• ≥ 50% stenosis in ≥ 2 coronary vessels or
• Diffuse atherosclerosis in a 3-vessel distribution
• Elevated coronary calcium score
• CAC \>100 + \>1 ASCVD risk factor
• CAC \>300
• If the patient is on a statin they must be on a stable dose for at least 3 months prior to enrollment.

You may not qualify if:

• 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:

Sponsors & Collaborators

• Brigham and Women's Hospital: lead

Study Sites (1)

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

RECRUITING

MeSH Terms

Interventions

evolocumab

Study Officials

• Diana Lopez, MD

  Brigham and Women's Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Diana Lopez, MD

CONTACT

617-525-8268; dlopez@bwh.harvard.edu

Leanne Barrett

CONTACT

617-732-4719; lbarrett11@bwh.harvard.edu

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Cardiologist

Model Details: The study protocol is an open label pilot study with a parallel control group.

Study Record Dates

• First Submitted: November 29, 2021
• First Posted: December 10, 2021
• Study Start: March 3, 2022
• Primary Completion (Estimated): March 31, 2027
• Study Completion (Estimated): December 31, 2027
• Last Updated: November 4, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)