TY - JOUR
T1 - Incorporating a polygenic risk score-triaged coronary calcium score into cardiovascular disease examinations to identify subclinical coronary artery disease (ESCALATE)
T2 - Protocol for a prospective, nonrandomized implementation trial
AU - Gray, Michael P.
AU - Berman, Yemima
AU - Bottà, Giordano
AU - Grieve, Stuart M.
AU - Ho, Amy
AU - Hu, Jessica
AU - Hyun, Karice
AU - Ingles, Jodie
AU - Jennings, Garry
AU - Kilov, Gary
AU - Levesque, Jean Frederic
AU - Meikle, Peter
AU - Redfern, Julie
AU - Usherwood, Tim
AU - Vernon, Stephen T.
AU - Nicholls, Stephen J.
AU - Figtree, Gemma A.
AU - on behalf of the PPP-CAD Collaborators
N1 - Funding Information:
The study is funded by a National Health and Medical Research Council (NHMRC) Partnership grant (GNT2005790). The NHMRC is the statutory authority of the Australian Government responsible for medical research.
Funding Information:
The study is an investigator-initiated study supported by an NHMRC Partnerships award. No additional, extramural funding will be used to conduct the trial. Per funding guidelines, partner organizations must provide at least half the research budget for funded trials through cash and/or in-kind support. No cash support for the ESCALATE trial design and execution has been received from for-profit, commercial interests. 23Strands has committed to providing financial support for a nonposttrial investigators’ meeting. Allelica SRL (Italy), Castlereagh Imaging, North Shore Radiology & Nuclear Medicine, and Sonic Healthcare have provided in-kind support through reduced rates for trial services.
Funding Information:
The investigators are grateful to the participants who have donated their samples and time for the ESCALATE trial. We would additionally like to thank Dr Zara S. Ali and Tung Nguyen for central operational support of the study. We would finally like to thank clinical site staff for their leadership, including Vikki Meyer, Rachel Rowe, Bek Scott, and Lina Zhou. The ESCALATE trial is funded through the NHMRC partnership projects funding mechanism, supporting clinicians, researchers, consumers, policy makers, and members of industry to identify evidence gaps, design research studies to close these gaps, interpret findings, and implement into policy and practice. The authors would like to acknowledge the contributions of all partners in the partnership for precision prevention of coronary artery disease (GNT2005790): Allelica, Australian Cardiovascular Alliance, Baker Heart & Diabetes Institute, Bioplatforms Australia, The Broad Institute of MIT and Harvard, Bupa Australia, Heart Research Australia, iCoreLabs, Launceston Medical Center, Monash University, National Heart Foundation NSW, North Shore Radiology & Nuclear Medicine, NSW Agency for Clinical Innovation, Our Medical Home Crows Nest, Siemens Healthineers, Sonic Healthcare (Castlereagh Imaging, Sonic Pathology, & Sullivan Nicolaides Pathology), University of Melbourne, University of Sydney, Western Sydney Primary Health Network, 23Strands.
Publisher Copyright:
© 2023 The Author(s)
PY - 2023/10
Y1 - 2023/10
N2 - Background: Identifying and targeting established modifiable risk factors has been a successful strategy for reducing the burden of coronary artery disease (CAD) at the population-level. However, up to 1-in-4 patients who present with ST elevation myocardial infarction do so in the absence of such risk factors. Polygenic risk scores (PRS) have demonstrated an ability to improve risk prediction models independent of traditional risk factors and self-reported family history, but a pathway for implementation has yet to be clearly identified. The aim of this study is to examine the utility of a CAD PRS to identify individuals with subclinical CAD via a novel clinical pathway, triaging low or intermediate absolute risk individuals for noninvasive coronary imaging, and examining the impact on shared treatment decisions and participant experience. Trial Design: The ESCALATE study is a 12-month, prospective, multicenter implementation study incorporating PRS into otherwise standard primary care CVD risk assessments, to identify patients at increased lifetime CAD risk for noninvasive coronary imaging. One-thousand eligible participants aged 45 to 65 years old will enter the study, which applies PRS to those considered low or moderate 5-year absolute CVD risk and triages those with CAD PRS ≥80% for a coronary calcium scan. The primary outcome will be the identification of subclinical CAD, defined as a coronary artery calcium score (CACS) >0 Agatston units (AU). Multiple secondary outcomes will be assessed, including baseline CACS ≥100 AU or ≥75th age-/sex-matched percentile, the use and intensity of lipid- and blood pressure-lowering therapeutics, cholesterol and blood pressure levels, and health-related quality of life (HRQOL). Conclusion: This novel trial will generate evidence on the ability of a PRS-triaged CACS to identify subclinical CAD, as well as subsequent differences in traditional risk factor medical management, pharmacotherapy utilization, and participant experience. Trial Registration: Australian New Zealand Clinical Trials Registry, ACTRN12622000436774. Trial was prospectively registered on March 18, 2022. https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=383134
AB - Background: Identifying and targeting established modifiable risk factors has been a successful strategy for reducing the burden of coronary artery disease (CAD) at the population-level. However, up to 1-in-4 patients who present with ST elevation myocardial infarction do so in the absence of such risk factors. Polygenic risk scores (PRS) have demonstrated an ability to improve risk prediction models independent of traditional risk factors and self-reported family history, but a pathway for implementation has yet to be clearly identified. The aim of this study is to examine the utility of a CAD PRS to identify individuals with subclinical CAD via a novel clinical pathway, triaging low or intermediate absolute risk individuals for noninvasive coronary imaging, and examining the impact on shared treatment decisions and participant experience. Trial Design: The ESCALATE study is a 12-month, prospective, multicenter implementation study incorporating PRS into otherwise standard primary care CVD risk assessments, to identify patients at increased lifetime CAD risk for noninvasive coronary imaging. One-thousand eligible participants aged 45 to 65 years old will enter the study, which applies PRS to those considered low or moderate 5-year absolute CVD risk and triages those with CAD PRS ≥80% for a coronary calcium scan. The primary outcome will be the identification of subclinical CAD, defined as a coronary artery calcium score (CACS) >0 Agatston units (AU). Multiple secondary outcomes will be assessed, including baseline CACS ≥100 AU or ≥75th age-/sex-matched percentile, the use and intensity of lipid- and blood pressure-lowering therapeutics, cholesterol and blood pressure levels, and health-related quality of life (HRQOL). Conclusion: This novel trial will generate evidence on the ability of a PRS-triaged CACS to identify subclinical CAD, as well as subsequent differences in traditional risk factor medical management, pharmacotherapy utilization, and participant experience. Trial Registration: Australian New Zealand Clinical Trials Registry, ACTRN12622000436774. Trial was prospectively registered on March 18, 2022. https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=383134
UR - http://www.scopus.com/inward/record.url?scp=85171601158&partnerID=8YFLogxK
U2 - 10.1016/j.ahj.2023.06.009
DO - 10.1016/j.ahj.2023.06.009
M3 - Article
C2 - 37364748
AN - SCOPUS:85171601158
SN - 0002-8703
VL - 264
SP - 163
EP - 173
JO - American Heart Journal
JF - American Heart Journal
ER -
