Utility and Effectiveness of Polygenic Risk Scoring (PRS) for Coronary Artery Disease (CAD)

Not Applicable

• Conditions: Coronary Disease; Cardiovascular Diseases; Polygenic Risk Score; Coronary Artery Disease; Heart Diseases; Myocardial Infarction
• Interventions: Genetic: Disclosure of integrate risk score for coronary artery disease

• Registration Number: NCT06542432
• Lead Sponsor: MyOme

Brief Summary

The goal of this study is to assess the benefit to physicians and patients of adding an integrated risk score (IRS) to existing coronary artery risk tools by conducting a randomized prospective study. IRS combines both an individual's coronary artery disease (CAD) polygenic risk score (PRS) and clinical risk factors, like cholesterol levels and age. This study will examine to what extent IRS knowledge impacts physician/provider behavior as well as clinical outcomes including cholesterol levels and incident heart disease.

Detailed Description

This is a 1:1 randomized controlled trial of participants with no known coronary artery disease, are not on lipid-lowering therapy, and do not have LDL-C over 190mg/dL. Participants will be recruited from cohorts that have been previously genotyped and found to have either elevated or average risk based on a CAD IRS. Participants will be randomized into two equal groups: one group will receive their IRS result for coronary artery disease at baseline, and the other group will receive their ASCVD Pooled Cohorts Equation result at baseline and CAD IRS result approximately 3 years after enrollment. Subject data will be collected for 5 years from the time of enrollment.

Study Timeline

• Study First Submitted: 2024-03-29
• Study First Submitted QC: 2024-08-05
• Study First Posted: 2024-08-07
• Study Start: 2025-01-01
• Status Verified: 2025-02
• Last Update Submitted: 2025-02-27
• Last Update Posted: 2025-03-04
• Primary Completion: 2029-07-01
• Study Completion: 2029-07-01

Recruitment & Eligibility

• Status: ENROLLING_BY_INVITATION
• Sex: All
• Target Recruitment: 1000

Inclusion Criteria

• ASCVD risk ≥5% and below 20% over the following 10 years as defined by the standard pooled cohort equations
• No previous CAD event (inclusive of myocardial infarction, diagnosis of CAD, stroke)
• Previously genotyped as part of a research study that enables recontact of participants
• Receiving primary care at a participating institution.

Exclusion Criteria

• Prior diagnosis of CAD: inclusive of prior myocardial infarction and revascularization (stent or coronary artery bypass grafting)
• Currently treated with lipid-lowering therapy, including statins, ezetimibe, PCSK9 inhibitors, inclisiran, or bempedoic acid
• Future use of statins contraindicated
• Prior diagnosis of Cerebrovascular disease: Inclusive of history of ischemic stroke, transient ischaemic attack (TIA), carotid endarterectomy, carotid artery stenting
• Prior diagnosis of Peripheral arterial disease: Inclusive of history of claudication, revascularization (stents or bypass)
• Severe hypercholesterolemia (LDL-C ≥ 190 mg/dL)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Experimental: Intervention	Disclosure of integrate risk score for coronary artery disease	Participants will receive their integrated risk score result for coronary artery disease.

Primary Outcome Measures

Name	Time	Method
Does receiving an IRS report influence clinical decision making, including the provider's decision to treat with lipid lowering medication or order diagnostic testing?	5 years	Aggregating longitudinal clinical data will be collected to compare the incidence of lipid-lowering medication initiation and cardiac diagnostic testing between the intervention arm which received their integrated risk score and the control group.
Does receiving an IRS report affect patient clinical measurements, including LDL-C levels?	5 years	Aggregating longitudinal clinical data will be collected to compare the clinical measurements between the intervention arm which received their integrated risk score and the control group.

Secondary Outcome Measures

Name	Time	Method
Does receiving an IRS report affect participant understanding of their individual CAD risk?	5 years	Patient survey data will be collected to assess their understanding of their CAD risk.
Does receiving an IRS report affect the incidence of CAD events?	5 years	Aggregated longitudinal clinical data will be collected to compare patient clinical outcomes in those with a CAD IRS reported at baseline and the control group.
Does the IRS identify those at elevated risk for CAD and future ASCVD events?	5 years	Aggregated longitudinal clinical data and patient survey data will be collected to compare patient clinical outcomes in those with a high CAD IRS.

Trial Locations

Locations (1)

University of Pennsylvania; 🇺🇸 Philadelphia, Pennsylvania, United States