Key result
Upfront statin plus ezetimibe linked to ~6.2-fold higher odds of meeting LDL-C targets in ACS.
Why the study?
The 2025 ESC/EAS Focused Update recommends initiating combination high-intensity statin plus ezetimibe during ACS hospitalization for LLT-naive patients with high baseline LDL-C, motivating an evaluation of patient eligibility and real-world efficacy in achieving the <55 mg/dL target.
Does upfront combination therapy with high-intensity statin plus ezetimibe improve achievement of the <55 mg/dL LDL-C target at 3 months compared to statin monotherapy in lipid-lowering therapy-naive acute coronary syndrome patients with admission LDL-C >110 mg/dL?
Observational (n=923)
No
Does upfront combination therapy with high-intensity statin plus ezetimibe improve achievement of the <55 mg/dL LDL-C target at 3 months compared to statin monotherapy in lipid-lowering therapy-naive acute coronary syndrome patients with admission LDL-C >110 mg/dL?
In lipid-lowering therapy-naive ACS patients with baseline LDL-C >110 mg/dL, upfront combination therapy with a high-intensity statin plus ezetimibe more than doubles the rate of achieving the <55 mg/dL LDL-C goal at 3 months compared to statin monotherapy, validating the 2025 ESC/EAS guideline recommendations.
Ezetimibe addition was associated with higher LDL-C target attainment in ACS; supports 2025 ESC/EAS recommendation but leaves open randomized confirmation.
Background The 2025 ESC/EAS Focused Update on the Management of Dyslipidaemias recommends initiating combination therapy with a high-intensity statin plus ezetimibe during the index hospitalization for acute coronary syndrome (ACS) in lipid-lowering therapy (LLT)-naive patients unlikely to achieve LDL-C goals with monotherapy. This Class IIa recommendation upgrades the previous IIb advice, targeting patients with high baseline LDL-C levels. Purpose This study aims to identify the proportion of ACS patients eligible for this upfront strategy specifically based on high admission LDL-C, and to evaluate its real-world efficacy in achieving the therapeutic target (<55 mg/dL). Methods This is a prospective, observational, single-centre study of consecutive ACS patients from the CARTACS registry. We analyzed 923 patients admitted for ACS with confirmed coronary disease and Friedewald-calculated in-hospital LDL-C measurements between July 2023 and August 2025. "LDL-driven Predicted Monotherapy Failure" (LDL-PMF) was defined as an admission LDL-C >110 mg/dL in LLT-naive patients, representing the threshold where the expected ≈50% reduction from high-intensity statin monotherapy fails to reach the <55 mg/dL target. A binary logistic regression model was used to identify independent predictors of achieving the LDL-C target after 3 months of follow-up. Results A total of 444 patients (48%) were LLT-naive. Within this naive cohort, 211 (48%) met the criteria for LDL-PMF (LDL-C >110 mg/dL). In this specific subgroup, 85 (40%) received statin monotherapy, 124 (59%) received combination therapy (high-intensity statin + ezetimibe) at discharge, and 2 (1%) received alternative LLT regimens. Patients on combination therapy achieved significantly lower follow-up LDL-C levels (47 [39–62] vs. 65 [55–86] mg/dL; p < 0.001) and a higher rate of target achievement (65% vs. 27%; p < 0.001) than those on monotherapy. In the multivariable analysis (Table), ezetimibe use was the strongest independent predictor of reaching the target (OR 6.17, 95% CI: 2.78–13.71; p < 0.001). Conclusions Nearly half of LLT-naive ACS patients are at high risk of monotherapy failure based on their high admission LDL-C levels. Our findings strongly support the 2025 ESC/EAS Guidelines update: in patients with LDL-PMF, adding ezetimibe to high-intensity statins at discharge significantly increases the likelihood of achieving the <55 mg/dL target compared to monotherapy.TableFigure
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Hernandez et al. (2026) conducted an observational in Acute coronary syndrome (ACS) with high admission LDL-C (>110 mg/dL) (n=923). Upfront combination therapy (high-intensity statin plus ezetimibe) vs. Statin monotherapy was evaluated on Achievement of LDL-C therapeutic target (<55 mg/dL) at 3 months (OR 6.17, 95% CI 2.78-13.71, p=< 0.001). Upfront high-intensity statin plus ezetimibe in LLT-naive ACS patients with LDL-C >110 mg/dL increased target (<55 mg/dL) achievement vs monotherapy (65% vs 27%; OR 6.17, 95% CI 2.78-13.71; p<0.001).
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