European and US guideline-based statin eligibility, genetically predicted coronary artery disease, and the risk of major coronary events

Abstract

Abstract Objectives To investigate whether polygenic risk score for coronary artery disease (CAD-PRS) can guide the initiation of lipid-lowering treatment as well as deferral beyond the statin eligibility criteria. Methods 311,799 individuals aged 40 to 73 years and free of atherosclerotic cardiovascular disease (ASCVD), diabetes, chronic kidney disease, and lipid-lowering treatment at baseline were included from the UK Biobank. Participants were categorized by statin eligibility using the European and US guidelines on statin use. Results For a median (IQR) follow-up of 11.9 (11.2-12.6) years, 8,196 individuals experienced major coronary events. CAD-PRS added to European-SCORE2 and US-PCE models identified 18% and 12% of individuals with class II indication for statin use whose risk of major coronary events were same or higher than the average risk of those with class I indication and 16% and 12% of individuals with class I indication whose major coronary event risks were same or lower than the average risk of those with class II indication. For ASCVD events, CAD-PRS added to European-SCORE2 and US-PCE models resulted in a net reclassification improvement of 13.6% (95% CI 11.8 to 15.5) and 14.7% (95% CI 13.1 to 16.3) among class I indicated, 10.8% (95% CI 9.6 to 12.0) and 15.3% (95% CI 13.2 to 17.5) among class II indicated, and 0.9% (95% CI 0.6 to 1.3) and 3.6% (95% CI 3.0 to 4.2) among class III indicated individuals. Conclusions CAD-PRS may guide statin initiation as well as deferral among individuals with class I and class II indication for statin use as defined by the European and US guidelines. However, the CAD-PRS had little clinical utility among individuals who were not eligible for statins.