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

NCT06542432 | Enrolling By Invitation

• 1 other identifier: 004
• Study Type: interventional
• Target: 1,000
• Locations: 1 country
• Sites: 2

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.

Conditions

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

Keywords

Polygenic risk score; Integrated risk score; Genetics; Cardiovascular health; Coronary artery disease; Precision medicine

Outcome Measures

Primary Outcomes (2)

• Does receiving an IRS report influence clinical decision making, including the provider's decision to treat with lipid lowering medication or order diagnostic testing?

  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.

  5 years

• Does receiving an IRS report affect patient clinical measurements, including LDL-C levels?

  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.

  5 years

Secondary Outcomes (3)

• Does the IRS identify those at elevated risk for CAD and future ASCVD events?

  5 years

• Does receiving an IRS report affect the incidence of CAD events?

  5 years

• Does receiving an IRS report affect participant understanding of their individual CAD risk?

  5 years

Study Arms (2)

Experimental: Intervention

EXPERIMENTAL

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

Genetic: Disclosure of integrate risk score for coronary artery disease

No Intervention: Control

NO INTERVENTION

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.

Interventions

Disclosure of integrate risk score for coronary artery disease GENETIC

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

Experimental: Intervention

Eligibility Criteria

• Age: 40 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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)

Sponsors & Collaborators

• MyOme: lead
• University of Pennsylvania: collaborator
• Mayo Clinic: collaborator

Study Sites (2)

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

MeSH Terms

Conditions

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

Condition Hierarchy (Ancestors)

Myocardial Ischemia; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Genetic Predisposition to Disease; Disease Susceptibility; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Infarction; Ischemia; Necrosis

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 29, 2024
• First Posted: August 7, 2024
• Study Start: January 1, 2025
• Primary Completion (Estimated): July 1, 2029
• Study Completion (Estimated): July 1, 2029
• Last Updated: September 16, 2025

Record last verified: 2025-09

Locations

US (2)