European and US Guideline‐Based Statin Eligibility, Genetically Predicted Coronary Artery Disease, and the Risk of Major Coronary Events

Abstract

Background A study was designed to investigate whether the coronary artery disease polygenic risk score (CAD‐PRS) may guide lipid‐lowering treatment initiation as well as deferral in primary prevention beyond established clinical risk scores. Methods and Results Participants were 311 799 individuals from the UK Biobank free of atherosclerotic cardiovascular disease, diabetes, chronic kidney disease, and lipid‐lowering treatment at baseline. Participants were categorized as statin indicated, statin indication unclear, or statin not indicated as defined by the European and US guidelines on statin use. For a median of 11.9 (11.2–12.6) years, 8196 major coronary events developed. CAD‐PRS added to European‐Systematic Coronary Risk Evaluation 2 (European‐SCORE2) and US‐Pooled Cohort Equation (US‐PCE) identified 18% and 12% of statin‐indication‐unclear individuals whose risk of major coronary events were the same as or higher than the average risk of statin‐indicated individuals and 16% and 12% of statin‐indicated individuals whose major coronary event risks were the same as or lower than the average risk of statin‐indication‐unclear individuals. For major coronary and atherosclerotic cardiovascular disease events, CAD‐PRS improved C‐statistics greater among statin‐indicated or statin‐indication‐unclear than statin‐not‐indicated individuals. For atherosclerotic cardiovascular disease events, CAD‐PRS added to the European evaluation and US equation resulted in a net reclassification improvement of 13.6% (95% CI, 11.8–15.5) and 14.7% (95% CI, 13.1–16.3) among statin‐indicated, 10.8% (95% CI, 9.6–12.0) and 15.3% (95% CI, 13.2–17.5) among statin‐indication‐unclear, and 0.9% (95% CI, 0.6–1.3) and 3.6% (95% CI, 3.0–4.2) among statin‐not‐indicated individuals. Conclusions CAD‐PRS may guide statin initiation as well as deferral among statin‐indication‐unclear or statin‐indicated individuals as defined by the European and US guidelines. CAD‐PRS had little clinical utility among statin‐not‐indicated individuals.