Integrating a Polygenic Risk Score for Coronary Artery Disease as a Risk Enhancing Factor in the Pooled Cohort Equation is Cost-effective in a US Health System
Authors: Mujwara Deo , Henno Geoffrey , Vernon Stephen T , Peng Siyang , Di Domenico Paolo , Schroeder Brock , Busby George B , Figtree Gemma A , Bottà Giordano 
Published: June 2021

AbstractImportanceThe pooled cohort equation (PCE) is used to determine an individual’s 10-year risk (low, borderline, intermediate, or high) of atherosclerotic cardiovascular disease (ASCVD) but it fails to identify all individuals at high risk. Those with borderline or intermediate risk require additional risk enhancing factors to guide preventive therapy decisions. Including a polygenic risk score (PRS) for coronary artery disease as a risk enhancing factor improves precision in determining the risk of ASCVD and informs decisions for prevention therapy.ObjectiveTo assess the cost-effectiveness of integrating PRS for coronary artery disease with the PCE to determine an individual’s 10-year risk for ASCVD compared to the PCE-alone.Design, setting, and populationA Markov model was developed on a hypothetical cohort of 40-year-old individuals in the US with borderline or intermediate PCE 10-year risk for ASCVD who fall in the top quintile of the PRS distribution and are not on preventive therapy (e.g., statins). Model transition probabilities and economic costs came from existing literature with costs reflecting a payer perspective and inflation-adjusted to 2019 US$.InterventionsThe modeled strategies were: (1) the PCE-alone and (2) the PCE with PRS for coronary artery disease as a risk enhancing factor. Analyses were performed at 5 year, 10 year, and lifetime time horizons.Main outcomes and measuresQuality-adjusted life-years (QALYs) gained, acute coronary syndromes and ischemic stroke events prevented, mean costs, and incremental cost-effectiveness ratios (ICER) were measured. One-way, two-way, and probabilistic sensitivity analyses were used to assess uncertainty in parameter estimates. Future costs and health benefits were discounted at an annual rate of 3%.ResultsCompared to the PCE-alone, PCE+PRS was cost-saving, effective and cost-effective (dominant). A health system would save more than $500, $2,300, and $9,000 per additional high-risk individual identified using PCE+PRS and prevent 27, 47 and 83 acute CAD or ischemic stroke events per 1,000 persons in 5 year, 10 year, and lifetime time horizons, respectively.Conclusions and relevanceImplementing PRS as a risk enhancing factor for CAD among individuals with borderline or intermediate 10-year risk reclassifies individuals as high-risk who would otherwise remain unidentified, prevents future acute CAD and ischemic stroke events, and both saves money and is cost-effective for health systems.Key PointsQuestionIs it cost-effective to use polygenic risk scores (PRS) for coronary artery disease (CAD) among individuals with borderline or intermediate risk of atherosclerotic cardiovascular disease (ASCVD) to inform preventive therapy decisions?FindingsWe modeled a hypothetical cohort of individuals with borderline or intermediate risk of ASCVD who fall in the top quintile of the CAD-PRS distribution but not on preventive therapy. Integrating CAD-PRS in the pooled cohort equation improved quality-adjusted life-years, saved money and was cost-effective.MeaningIntegrating PRS as an enhancing factor in the pooled cohort equation risk assessment for ASCVD used in current clinical practice was cost-effective.