Cost-Effectiveness of Polygenic Risk Score–Guided Statin Therapy for Cardiovascular Disease Prevention in Singapore

BACKGROUND: Atherosclerotic cardiovascular disease (ASCVD) is a leading cause of morbidity and mortality in Singapore. Under current guidelines, individuals at intermediate risk often do not receive preventive statin therapy despite potentially elevated genetic risk. Polygenic risk scores (PRSs) offer an opportunity to refine risk stratification, but their economic value in Asian health care settings remains uncertain. OBJECTIVES: The authors aimed to evaluate the cost-effectiveness of PRS-guided risk assessment for a cohort of 45-year-old Singapore residents with intermediate (7.5%-20%) 10-year ASCVD risk. METHODS: We developed a state-transition Markov model comparing 2 strategies: 1) standard risk assessment using the pooled cohort equation, with statin initiation based on traditional risk factors; and 2) PRS-guided reclassification, with statin therapy initiated for individuals in the top 20% of the PRS distribution. Model inputs were derived from the literature as well as local registry data. Outcomes were evaluated from the health care payer perspective over 2- to 40-year horizons. Deterministic and probabilistic sensitivity analyses were conducted. RESULTS: PRS-guided therapy was not cost-effective over 2- to 20-year horizons. From 30 years onward, it became cost-effective (Singapore dollars [SGD]) at a willingness-to-pay threshold of SGD 75,000/quality-adjusted life year (QALY), with an incremental cost-effectiveness ratio of SGD 60,334/QALY at 30 years and SGD 23,667/QALY at 40 years. Probabilistic analysis showed a 53.5% probability of cost-effectiveness, with mean incremental cost and effectiveness of SGD 292 (95% uncertainty interval [UI]: -SGD 490 to SGD 1,052) and 0.010 QALYs (95% UI: -0.062 to 0.087), respectively. CONCLUSIONS: Incorporating PRS into ASCVD risk stratification for intermediate-risk individuals in Singapore may represent a cost-effective long-term prevention strategy as benefits of avoided ASCVD events accumulate.