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