NCT05152888

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

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

• Status: Recruiting
• Phase: Phase 4
• Study type: Interventional
• Enrollment: 50 (estimated)
• Sponsor: Brigham and Women's Hospital · Academic / Other
• Sex: All
• Age: 50 Years – 90 Years
• Healthy volunteers: Not accepted

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.

Detailed description

The investigators propose an open-label investigator-initiated trial to directly test whether PCSK-9 inhibition with Evolocumab in patients with stable CAD improves PET CFR and stress MBF. To further elucidate the possible mechanisms by which myocardial blood flow improves with PCSK-9 inhibition, the investigators will assess changes in inflammatory biomarkers. The findings of this translational study will provide a physiological read-out of the comprehensive effects of Evolocumab on tissue perfusion and microvascular function in a high-risk population. As such, these data would serve to provide a mechanistic explanation for why Evolocumab may reduce cardiovascular events beyond a reduction in plaque burden and composition. The central hypothesis of this study is that PCSK-9 inhibition will quantitatively improve myocardial blood flow as measured by positron emission tomography (PET) in patients with stable coronary artery disease. The investigators postulate that the improvement in myocardial blood flow will correlate with a reduction in inflammatory biomarkers, and not simply an improvement in coronary epicardial plaque burden.

Conditions

• Stable Coronary Disease

Interventions

Type	Name	Description
DRUG	Evolocumab	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.

Timeline

• Start date: 2022-03-03
• Primary completion: 2027-03-31
• Completion: 2027-12-31
• First posted: 2021-12-10
• Last updated: 2025-11-04

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study