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

NCT ID: NCT06542432

Last Updated: 2025-09-16

Basic Information

• Recruitment Status: ENROLLING_BY_INVITATION
• Clinical Phase: NA
• Total Enrollment: 1000 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-01-01
• Study Completion Date: 2029-07-01

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.

Conditions

Coronary Artery Disease; Polygenic Risk Score; Heart Diseases; Coronary Disease; Myocardial Infarction; Cardiovascular Diseases

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: SINGLE

Study Groups

Experimental: Intervention

Participants will receive their integrated risk score result for coronary artery disease.

Group Type: EXPERIMENTAL

Disclosure of integrate risk score for coronary artery disease

Intervention Type: GENETIC

Participants will receive their integrated risk score for coronary disease along with an optional genetic counseling visit to discuss the results.

No Intervention: Control

Participants will only receive standard of care ASCVD Pooled Cohorts Equation (ASCVD PCE), and disclosure of integrated risk score result will be deferred until 3 years after enrollment.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Disclosure of integrate risk score for coronary artery disease

Participants will receive their integrated risk score for coronary disease along with an optional genetic counseling visit to discuss the results.

Intervention Type: GENETIC

Eligibility Criteria

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)

• Minimum Eligible Age: 40 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Pennsylvania

OTHER

Sponsor Role: collaborator

Mayo Clinic

OTHER

Sponsor Role: collaborator

MyOme

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Mayo Clinic

Rochester, Minnesota, United States

University of Pennsylvania

Philadelphia, Pennsylvania, United States

Countries

United States

Other Identifiers

004

Identifier Type: -

Identifier Source: org_study_id