Polygenic Risk Scoring for Coronary Artery Disease

Enrolling by invitation at 1 trial location

Overseen By Lindsay Meyers, MS

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: MyOme

Must not be taking: Statins, Ezetimibe, PCSK9 inhibitors

Disqualifiers: CAD, Cerebrovascular disease, Peripheral arterial disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 1

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines how an Integrated Risk Score (IRS) might assist doctors and patients in understanding heart disease risk. The IRS combines genetic information with common risk factors, such as cholesterol levels. The study evaluates whether knowing the IRS influences doctors' decisions and impacts heart health. Potential participants are individuals without prior heart issues but with a moderate risk of developing heart disease in the next ten years. Participants will receive their IRS results either immediately or after three years. As an unphased study, this trial allows participants to contribute to innovative research that could enhance heart disease prevention strategies.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it excludes people who are currently treated with lipid-lowering therapy like statins. This suggests that if you are on such medications, you may not be eligible to participate.

What prior data suggests that this integrated risk score is safe for assessing coronary artery disease risk?

Research has shown that sharing an integrated risk score (IRS) with individuals at risk for coronary artery disease is generally safe. The IRS combines a person's genetic risk score, known as a polygenic risk score (PRS), with traditional health factors like cholesterol levels and age.

In past studies, individuals who learned about their IRS did not report any major safety issues. One study found that those who received their IRS experienced fewer major heart-related problems compared to those who did not. This suggests that knowing their risk score did not cause harm and might even improve health outcomes.

The IRS is not a drug or a new medical procedure. It assesses risk, so it lacks the usual side effects associated with medication. This distinguishes it from many other clinical trial treatments. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it explores using polygenic risk scoring to predict coronary artery disease (CAD) risk more accurately than traditional methods. Unlike the standard ASCVD Pooled Cohorts Equation, which primarily considers factors like age, cholesterol levels, and blood pressure, the Integrated Risk Score (IRS) includes genetic data, offering a personalized risk assessment. This could lead to earlier and more precise interventions, potentially preventing CAD before it develops.

What evidence suggests that the Integrated Risk Score is effective for coronary artery disease?

Studies have shown that polygenic risk scores (PRS) can help doctors better predict the likelihood of developing coronary artery disease (CAD). When combined with traditional risk factors like cholesterol levels and age, PRS makes it easier to assess a person's risk of heart disease over the next 10 years. This trial will evaluate the effectiveness of providing participants with their integrated risk score (IRS) for coronary artery disease. This combined approach helps doctors make more informed decisions about treatment and management. Specifically, previous patients with medium risk levels benefited from this method. Overall, the integrated risk score (IRS) seems to improve risk prediction and could lead to better outcomes for patients. ^{1 3 5 6 7}

Are You a Good Fit for This Trial?

This trial is for individuals with a moderate risk of heart disease in the next 10 years, who have been previously genotyped for research and are receiving care at a participating institution. It's not open to those who've already had a heart-related event like a heart attack or stroke.

Inclusion Criteria

My risk of heart disease or stroke is between 5% and 20% over the next 10 years.

I receive my primary care from a participating institution.

I was genotyped in a study that allows follow-up contact.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline Assessment

Participants receive their integrated risk score result for coronary artery disease or standard of care ASCVD Pooled Cohorts Equation

1 visit

1 visit (in-person)

Follow-up

Participants are monitored for clinical outcomes and understanding of CAD risk over time

5 years

Annual visits (in-person or virtual)

Deferred Disclosure

Control group receives their integrated risk score result approximately 3 years after enrollment

3 years

What Are the Treatments Tested in This Trial?

Interventions

• Integrated Risk Score (IRS)

Trial Overview The study tests whether adding an integrated risk score (IRS), which combines genetic and clinical factors, to current coronary artery disease risk tools helps doctors make better treatment decisions and improves patient outcomes.

How Is the Trial Designed?

Group I: Experimental: Intervention Experimental Treatment 1 Intervention

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

Group II: No Intervention: Control Active Control 1 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.

Who Is Running the Clinical Trial?

MyOme

Lead Sponsor

Trials

1

Recruited

1,000+

University of Pennsylvania

Collaborator

Trials

2,118

Recruited

45,270,000+

Mayo Clinic

Collaborator

Trials

3,427

Recruited

3,221,000+

Published Research Related to This Trial

Recent advancements in identifying genetic alleles linked to coronary artery disease have led to improved polygenic risk scores, which can predict the likelihood of developing the disease and inform treatment responses.

The review highlights the importance of careful validation and responsible clinical use of these polygenic risk scores for risk prediction, patient prioritization, and enhancing clinical trial designs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical utility of polygenic risk scores for coronary artery disease. Klarin, D., Natarajan, P.[2023]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06542432

NCT06542432 | Utility and Effectiveness of Polygenic Risk ... 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 ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12331499/

Impact of polygenic risk score (PRS) for coronary artery ... This study aims to evaluate whether an AI-generated CAD risk profile that integrates PRS with traditional coronary risk factors can ...

3. mayo.edu mayo.edu/research/clinical-trials/cls-20579583

Utility and Effectiveness of Polygenic Risk Scoring (PRS) ... This study aims to identify how useful polygenic risk score (PRS) and integrated risk scoring (IRS) is in both helping doctors to treat and manage their ...

4. ahajournals.org ahajournals.org/doi/10.1161/JAHA.121.025236

Integrating a Polygenic Risk Score for Coronary Artery ... Polygenic risk score for coronary artery disease (CAD‐PRS) improves precision in determining the 10-year risk of atherosclerotic cardiovascular disease.

5. nature.com nature.com/articles/s44325-025-00049-7

Polygenic risk scores improve CAD risk prediction in ... This study assessed a risk model integrating PRS across populations, focusing on individuals with borderline/intermediate clinical risk.

6. ahajournals.org ahajournals.org/doi/abs/10.1161/CIRCGEN.124.004968

Effect of Disclosing a Polygenic Risk Score for Coronary ... Disclosure of an integrated risk score that included a polygenic risk score to individuals at intermediate risk for CHD was associated with lower MACE ...

7. jamanetwork.com jamanetwork.com/journals/jamacardiology/fullarticle/2800101

Predictive Utility of a Coronary Artery Disease Polygenic ... A PRS for CAD carried significantly greater predictive power in younger adults, contributing up to 30% of the myocardial infarction risk in this cohort.