Cost-Effectiveness Analysis of an Adjusted Polygenic Risk Score in Cardiovascular Disease Prevention

OBJECTIVES: Cardiovascular diseases (CVDs) remain the leading cause of morbidity and mortality globally. Although early identification of individuals at high risk and effective preventive interventions are crucial for reducing CVD burden, it is evident that current clinical tools may underestimate CVD risk. Recent advancements in genomics have led to the development of Polygenic Risk Score (PRS) as a promising tool for assessing genetic susceptibility to CVD. Combined with traditional clinical risk prediction metrics, adjusted PRS could revolutionize CVD prevention through screening, monitoring, and clinical management.

METHODS: A decision-analytic model was constructed to simulate the long-term health and economic outcomes associated with Adjusted PRS-guided prevention compared to standard of care. The model incorporated data on CVD incidence, mortality, healthcare costs, and quality-adjusted life years (QALYs) from national and international sources. Key inputs, including Adjusted PRS test accuracy, intervention efficacy, and resource utilization, were derived from the literature, Greek cost data sources, and from a panel of cardiology experts. A lifetime horizon and a healthcare payer's perspective were adopted.

RESULTS: The results of the cost-effectiveness analysis demonstrated that implementing Adjusted PRS-guided prevention strategies in Greece was cost-effective, compared to standard care alone. The Adjusted PRS-guided approach led to reductions in CVD events and cardiovascular-related deaths, resulting in gains in QALYs. Additionally, incremental cost-effectiveness ratios (ICERs) were below the commonly accepted willingness-to-pay thresholds, indicating good value for money. Sensitivity analyses confirmed the robustness of the findings.

CONCLUSIONS: Incorporating Adjusted PRS into routine clinical practice as a tool for risk stratification and preventive interventions for CVD is economically favorable and has the potential to enhance prevention efforts and reduce the burden of CVD. Further research is warranted to validate the clinical utility and long-term effectiveness of Adjusted PRS and support the feasibility of large-scale implementation.