Background and aims: 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. Methods and results: 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). Conclusions: 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.
Extreme cardiovascular risk as a major barrier to LDL-C target achievement: insights from ITACARE-P registry / Giallauria, F., Cuomo, G., Faggiano, A., Vallefuoco, G., Ambrosetti, M., Mureddu, G., Venturini, E., Ruzzolini, M., Gualeni, A., Vatri, M., Maranta, F., Maloberti, A., Carugo, S., Fattirolli, F., Faggiano, P.. - In: NMCD. NUTRITION METABOLISM AND CARDIOVASCULAR DISEASES. - ISSN 0939-4753. - ELETTRONICO. - (2026), pp. 105010.0-105010.0. [10.1016/j.numecd.2026.105010]
Extreme cardiovascular risk as a major barrier to LDL-C target achievement: insights from ITACARE-P registry
Vatri, Marco;Fattirolli, Francesco;
2026
Abstract
Background and aims: 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. Methods and results: 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). Conclusions: 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.
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