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

Abstract

ImportanceThe 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.

Longitudinal Genome-Wide Association Study of Cognitive Impairment after Subarachnoid Hemorrhage

“…A strong role of genetics or genomics in the disease etiology may even imply that patients or subjects with a high PRS benefit less from lifestyle changes, such as nutritional modification or smoking cessation, than those with a low PRS. Moreover, the advantages of earlier or more frequent screening using a reliable PRS-based panel will be able to reduce potential side effects such as life-threatening injuries occurring from radiation exposure, unnecessary screening, overdiagnosis, and neuro-degenerative distress after rupture symptoms [34].…”

Genomic Innovation in Early Life Cardiovascular Disease Prevention and Treatment

“…118 Results of studies examining the added predictive value of a CVD PRS to such equations have been mixed. 77,78,[119][120][121] For example, in a recent largescale observational study of 352 660 individuals, Elliott et al 77 122,123 Likewise, several studies have directly shown that PRS perform better among participants <50 years. 122,124 In aggregate, we expect that as PRS methods are further developed and derivation GWAS cohorts increase in size and diversity, PRS will consistently demonstrate added predictive value to current risk equations, particularly in younger age groups.…”

Using Multi-Ancestry Polygenic Risk Scores for Coronary Artery Disease as Risk Enhancers for a 10 Year Cardiovascular Risk Assessment Tool

“…(5-7.5%) or intermediate (7.5-20%) 10 year risk (BIR), additional Risk Enhancers can be used to further refine risk mitigation discussions between physician and patient, and PRSs have recently been proposed to aid clinical management of ASCVD in such discussions [25,28] while reducing healthcare costs from a payer's perspective [29]. We therefore sought to assess the potential for the multi-ancestry PRSs to be used as a discriminatory risk enhancing factor for CAD by using a two-fold increased risk threshold to identify individuals at high risk of CAD.…”

“…We show here that multi-ancestry CAD PRSs can play such a role by reclassifying significant proportions of individuals at increased risk of disease because of their genetics, but who are invisible and therefore missed by current ASCVD risk assessments, but who nevertheless go on to have disease. These PRSs are validated and calibrated on US populations and given their demonstrated cost-effectiveness [29,41] it is increasingly clear that they satisfy the criteria to be considered a Risk Enhancing Factor in the management of ASCVD risk.…”