Prospective Electronic Polygenic Risk Study

Study Overview
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Brief Summary
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This study will investigate the role of polygenic risk scores (PRS) in preventive health.

Detailed Description
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This study will investigate the role of polygenic risk scores (PRS) in preventive health. Specifically, the purpose of this study is to determine whether knowledge of the degree of coronary artery disease (CAD) genetic risk, as measured and conveyed by a PRS, influences patient and physician decision-making during short-term (6 month) and long-term (2 year) follow-up. The initial findings of this study will be used to plan an expanded second phase study with the purpose of prospectively validating that these decision-making changes lead to improvements in clinical outcomes.

Official Title
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Prospective Electronic Polygenic Risk Study (PEPRS) - First Phase

Conditions
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Coronary Artery Disease

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 45 ≥ Age < 65 ASCVD Risk Score > 7.5% as defined by the standard pooled cohort equation Access to and ability to use a smartphone Exclusion Criteria: Prior diagnosis of coronary disease as defined by prior myocardial infarction (STEMI or NSTEMI), or revascularization (stent or coronary artery bypass grafting) Cerebrovascular disease with history of ischemic stroke, TIA, carotid endarterectomy, carotid artery stenting Peripheral arterial disease with history of claudication, revascularization (stents or bypass) Current and active high-intensity statin prescription (rosuvastatin 20 mg, rosuvastatin 40 mg, atorvastatin 40 mg and atorvastatin 80 mg) Anti-PCSK9 therapy Lipid apheresis therapy Currently enrolled in a clinical trial for lipid lowering therapy Known statin intolerance to 2 or more statins in the past

Ages Eligible for Study
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Minimum Age: 45 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Subjects receiving care from Scripps Health physicians in Cardiology and Primary Care<br>A confidential data request will be submitted to screen the Scripps Health EHR system for individuals meeting study inclusion criteria and having seen a participating study physician in the past two years. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Statin or other lipid lowering therapy initiation or intensification by EHR entry | New or intensified prescriptions for statins or other LDL lowering therapy. Binary outcome measured at 6-months post-enrollment by survey-based self-report and EHR analysis - encoded as 0 if no new or intensified prescription relative to medication status at baseline, and 1 if a new or intensified prescription is entered in the EHR relative to medication status at baseline. A prescription for statins or other LDL lowering therapy is considered new if an EHR entry for a statin, PCSK9i, or ezitimibe is present at follow-up and no equivalent EHR entry exists for up to 1-year prior to enrollment. A statin prescription is considered intensified if an active statin prescription is present in the EHR at enrollment and an active statin prescription of a higher intensity tiers (high-, moderate-, and low-intensity) as described in the 2013 ACC/AHA Guidelines on the Treatment of Blood Cholesterol is present at follow-up. | 6 months post enrollment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Statin or other lipid lowering therapy persistence by EHR entry | Statin or other lipid lowering therapy prescription renewal. Binary outcome measured at 2-years post-enrollment by EHR analysis. Statin persistence is defined as prescription renewal within 60 days of the end of the duration of an index statin prescription made after study enrollment | 2 years post enrollment | 
| Statin or other lipid lowering therapy adherence by EHR entry | Statin or other lipid lowering therapy prescription possession. Binary outcome measured at 2-years post-enrollment by EHR entry. Statin adherence is defined as prescription coverage of no less than 80% of the days between the index statin prescription and the end of the 2-year follow-up period | 2 years post enrollment | 
| Adequate LDL-C lowering - comparison of baseline and follow-up measures by lab test | Adequate LDL-C lowering. Adequate LDL-C lowering is defined as 30% or more reduction from baseline study measured LDL-C | 6 months and 2 years post enrollment | 
| Lifestyle changes by survey | Adoption of Healthy Lifestyle. Binary outcomes derived from baseline and 6-months post-enrollment by survey-based self-report. | 6 months post enrollment | 
| Physician Utility by survey | Physician confidence, perceived utility, and actions attributable to genomic testing. | 6 months and 1 year |