Intensified lipid-lowering strategies and their effect on atherogenic and metabolic markers in coronary artery disease: a prospective cohort study

BACKGROUND AND AIMS: To evaluate the effects of varying lipid-lowering therapy (LLT) strategies on lipid profiles and insulin resistance (IR) biomarkers in coronary artery disease (CAD) patients. METHODS AND RESULTS: This prospective observational study enrolled 1391 CAD patients receiving monotherapy (statin or ezetimibe), dual therapy (statin + ezetimibe), or triple therapy (dual + PCSK9 inhibitor) at discharge. After a median 1-year follow-up, attainment rates and changes in low-density lipoprotein cholesterol (LDL-C), apolipoprotein B (ApoB), non-high-density lipoprotein cholesterol (non-HDL-C), remnant cholesterol (RC), total cholesterol (TC), triglyceride-glucose (TyG) index, and atherogenic index of plasma (AIP) were assessed. Linear regression evaluated associations between LLT intensity and biomarker percent change, with subgroup and interaction analyses exploring effect modification by baseline characteristics. Triple therapy achieved the largest reductions in LDL-C (-62.9%), non-HDL-C (-57.5%), ApoB (-56.1%), RC (-45.1%), and TyG (-7.1%), followed by dual therapy. Higher LLT intensity was independently associated with greater reductions in LDL-C, non-HDL-C, and TC, with triple therapy outperforming dual therapy. Greater TyG reduction with triple therapy was significant in unadjusted but not adjusted analyses. In the triple therapy group, goal attainment of LDL-C, non-HDL-C, ApoB, and RC improved significantly from baseline (all P < 0.01). BMI significantly modified lipid-lowering effects, with greater LDL-C, non-HDL-C, and TC reductions in non-overweight/obese than in overweight/obese patients. CONCLUSION: Triple LLT was associated with more comprehensive control of atherogenic lipid markers, with a similar trend for IR markers. Notably, stratified intensification of LLT may support individualized risk-factor management in CAD, although cardiovascular outcome benefits require further validation.