Extreme cardiovascular risk as a major barrier to LDL-C target achievement: insights from ITACARE-P registry

Achieving low-density lipoprotein cholesterol (LDL-C) targets remains challenging in secondary cardiovascular prevention despite the availability of effective lipid-lowering therapies. The 2025 ESC/EAS dyslipidaemia guidelines introduced an "extreme cardiovascular risk" category requiring LDL-C levels <40 mg/dL, potentially increasing the difficulty of target attainment. We aimed to identify clinical and therapeutic predictors of LDL-C target achievement according to the 2025 ESC/EAS recommendations and estimate the probability of goal attainment across different risk categories and treatment strategies.

This sub-analysis of the multicentre ITACARE-P registry included 1904 outpatients with established atherosclerotic cardiovascular disease. Missing data were handled using multiple imputation, and stable predictors were selected through Elastic Net regularization across 20 imputed datasets. A multivariable generalized linear mixed-effects model was internally validated using 1000 bootstrap resamples. Overall, 38% of patients achieved guideline-recommended LDL-C targets. Independent predictors of target attainment included PCSK9 inhibitor therapy (OR = 7.65), high-intensity statins (OR = 4.73), ezetimibe (OR = 2.64), male sex (OR = 1.99), diabetes mellitus (OR = 1.99), coronary artery disease (OR = 2.73), participation in cardiac rehabilitation (OR = 1.81), and high physical activity (O = 1.54). Current smoking, prior dyslipidaemia, and longer disease duration were associated with lower odds of achievement. Very-high-risk patients were more likely to achieve LDL-C targets than extreme-risk patients (OR = 5.66). Predicted target attainment ranged from 9.8% to 88.6% according to treatment intensity and risk category. Model discrimination was good (optimism-corrected AUC = 0.782).

LDL-C target attainment under the 2025 ESC/EAS guidelines remains suboptimal, particularly among extreme-risk patients. Earlier therapeutic intensification and individualized lipid-lowering strategies may be necessary to improve real-world goal achievement.