Abstract 15339: CAD Polygenic Risk Score and Incident Complex Coronary Revascularization in Adults With Atherosclerosis

Abstract

Introduction: A CAD polygenic risk score (CAD PRS) was previously shown to predict major vascular events among patients with established ASCVD. Whether genetic risk can predict the need for complex coronary revascularization procedures, including complex PCI or CABG, has not been established. Methods: The FOURIER trial randomized 27,564 patients with established ASCVD to evolocumab or placebo with a median follow-up of 2.2 years. Of these, 14,298 had genotype data and were used in this analysis. The CAD PRS was previously derived in a CAD GWAS and includes 2,293,205 SNPs. Clinical records were reviewed for coronary revascularization events to determine procedural characteristics and coronary anatomy. Complex revascularization was defined as complex PCI [multivessel PCI, >3 lesions, >3 stents, total stent length >60mm, or bifurcation PCI] or CABG. Associations between the CAD PRS and revascularization events were analyzed by PRS quintile. Results: Patients with higher CAD PRS were significantly more likely to undergo complex coronary revascularization than those with low genetic risk (Q5 vs Q1: HR 1.71; 95% CI 1.23-2.37; P=0.002) (Fig A), with a greater than 2-fold higher risk of complex PCI (HR 2.11; 1.33-3.35) and a numerically higher risk of CABG (HR 1.28; 0.80-2.05). These findings were directionally consistent for the individual components of complex PCI, including multivessel PCI (HR 1.71; 0.97-3.00), > 3 lesions (HR 1.85; 0.73-4.68), > 3 stents (HR 3.77; 1.75-8.12), stent length >60 mm (HR 2.07; 0.88-4.87), and bifurcation PCI (HR 2.17; 0.39-11.98) (Fig B). Conclusions: Among patients with established ASCVD, a CAD PRS predicted incident complex coronary revascularization procedures. Genetic prediction of advanced coronary disease requiring specific complex interventions has not previously been shown, and these findings may have the potential to yield novel approaches for reducing the need for these high-risk and costly procedures.