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

Importance: The 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. Objective: To 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 population: A 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$. Interventions: The 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 measures: Quality-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%. Results: Compared 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 relevance: Implementing 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.