Clinical trial NCT05072275: Prospective Electronic Polygenic Risk Study
Official title: Prospective Electronic Polygenic Risk Study (PEPRS) - First Phase
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Coronary Artery Disease
Lead sponsor: Scripps Translational Science Institute
Sponsor class: OTHER
Collaborators: name: Illumina, Inc.
name: Quest Diagnostics-Nichols Insitute
First posted: 2021-10-08
Enrollment: 1000
Sex: ALL
Minimum age (years): 45
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: 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.

Brief summary: This study will investigate the role of polygenic risk scores (PRS) in preventive health.

Detailed description: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Statin or other lipid lowering therapy initiation or intensification by EHR entry
timeFrame: 6 months post enrollment
Secondary outcomes:
measure: Statin or other lipid lowering therapy persistence by EHR entry
timeFrame: 2 years post enrollment
measure: Statin or other lipid lowering therapy adherence by EHR entry
timeFrame: 2 years post enrollment
measure: Adequate LDL-C lowering - comparison of baseline and follow-up measures by lab test
timeFrame: 6 months and 2 years post enrollment
measure: Lifestyle changes by survey
timeFrame: 6 months post enrollment
measure: Physician Utility by survey
timeFrame: 6 months and 1 year
Other outcomes:
Locations:
Study officials:
References:
citation: Arnett DK, Blumenthal RS, Albert MA, Buroker AB, Goldberger ZD, Hahn EJ, Himmelfarb CD, Khera A, Lloyd-Jones D, McEvoy JW, Michos ED, Miedema MD, Munoz D, Smith SC Jr, Virani SS, Williams KA Sr, Yeboah J, Ziaeian B. 2019 ACC/AHA Guideline on the Primary Prevention of Cardiovascular Disease: Executive Summary: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol. 2019 Sep 10;74(10):1376-1414. doi: 10.1016/j.jacc.2019.03.009. Epub 2019 Mar 17.
citation: Sattar N, Preiss D, Murray HM, Welsh P, Buckley BM, de Craen AJ, Seshasai SR, McMurray JJ, Freeman DJ, Jukema JW, Macfarlane PW, Packard CJ, Stott DJ, Westendorp RG, Shepherd J, Davis BR, Pressel SL, Marchioli R, Marfisi RM, Maggioni AP, Tavazzi L, Tognoni G, Kjekshus J, Pedersen TR, Cook TJ, Gotto AM, Clearfield MB, Downs JR, Nakamura H, Ohashi Y, Mizuno K, Ray KK, Ford I. Statins and risk of incident diabetes: a collaborative meta-analysis of randomised statin trials. Lancet. 2010 Feb 27;375(9716):735-42. doi: 10.1016/S0140-6736(09)61965-6. Epub 2010 Feb 16.
citation: Macedo AF, Taylor FC, Casas JP, Adler A, Prieto-Merino D, Ebrahim S. Unintended effects of statins from observational studies in the general population: systematic review and meta-analysis. BMC Med. 2014 Mar 22;12:51. doi: 10.1186/1741-7015-12-51.
citation: Mega JL, Stitziel NO, Smith JG, Chasman DI, Caulfield M, Devlin JJ, Nordio F, Hyde C, Cannon CP, Sacks F, Poulter N, Sever P, Ridker PM, Braunwald E, Melander O, Kathiresan S, Sabatine MS. Genetic risk, coronary heart disease events, and the clinical benefit of statin therapy: an analysis of primary and secondary prevention trials. Lancet. 2015 Jun 6;385(9984):2264-2271. doi: 10.1016/S0140-6736(14)61730-X. Epub 2015 Mar 4.
citation: Khera AV, Emdin CA, Drake I, Natarajan P, Bick AG, Cook NR, Chasman DI, Baber U, Mehran R, Rader DJ, Fuster V, Boerwinkle E, Melander O, Orho-Melander M, Ridker PM, Kathiresan S. Genetic Risk, Adherence to a Healthy Lifestyle, and Coronary Disease. N Engl J Med. 2016 Dec 15;375(24):2349-2358. doi: 10.1056/NEJMoa1605086. Epub 2016 Nov 13.
citation: Stone NJ, Robinson JG, Lichtenstein AH, Bairey Merz CN, Blum CB, Eckel RH, Goldberg AC, Gordon D, Levy D, Lloyd-Jones DM, McBride P, Schwartz JS, Shero ST, Smith SC Jr, Watson K, Wilson PW; American College of Cardiology/American Heart Association Task Force on Practice Guidelines. 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2014 Jul 1;63(25 Pt B):2889-934. doi: 10.1016/j.jacc.2013.11.002. Epub 2013 Nov 12. No abstract available.
citation: Raebel MA, Schmittdiel J, Karter AJ, Konieczny JL, Steiner JF. Standardizing terminology and definitions of medication adherence and persistence in research employing electronic databases. Med Care. 2013 Aug;51(8 Suppl 3):S11-21. doi: 10.1097/MLR.0b013e31829b1d2a.