Comparative effectiveness of lipid-lowering regimens for achieving ESC LDL-cholesterol targets in acute coronary syndrome: a real-world cohort analysis

Background Current European Society of Cardiology/European Atherosclerosis Society (ESC/EAS) guidelines recommend aggressive low-density lipoprotein cholesterol (LDL-C) targets of <55 mg/dL for acute coronary syndrome (ACS) patients, with a more stringent target of <40 mg/dL for recurrent events. However, real-world achievement rates across different lipid-lowering regimens remain poorly characterized. Methods We analyzed 298 ACS patients with valid baseline LDL-C measurements (mean 99.7 ± 40.8 mg/dL) from a tertiary care cohort. We performed McNemar's tests to account for the paired nature of the data.We simulated LDL-C reduction with seven treatment regimens: low-intensity statin (25% reduction), moderate-intensity statin (35%), high-intensity statin (50%), low-intensity statin plus ezetimibe (40%), moderate-intensity statin plus ezetimibe (48%), high-intensity statin plus ezetimibe (65%), and triple therapy with high-intensity statin, ezetimibe, and PCSK9 inhibitor (85%). Target achievement rates were calculated for both <55 mg/dL and <40 mg/dL thresholds, with statistical comparisons performed using chi-squared and pairwise tests. Results The distribution of baseline LDL-C categories was as follows: 81 patients (27.2%) had baseline LDL-C <70 mg/dL, 76 patients (25.5%) had LDL-C 70-100 mg/dL, 63 patients (21.1%) had LDL-C 100-130 mg/dL, 43 patients (14.4%) had LDL-C 130-160 mg/dL, and 35 patients (11.7%) had LDL-C ≥160 mg/dL (Table 1). This distribution indicates substantial heterogeneity in baseline lipid profiles, with approximately one-quarter of patients having relatively well-controlled LDL-C at baseline and another quarter having markedly elevated levels requiring intensive therapy.High-intensity statin monotherapy achieved the <55 mg/dL target in 61.9% of patients, while the addition of ezetimibe increased achievement to 88.1% (χ² = 29.03, p < 0.0001). Triple therapy achieved 100% target attainment for <55 mg/dL (χ² = 12.07, p = 0.0005 vs. high-intensity statin plus ezetimibe). For the <40 mg/dL target, achievement rates were 38.1%, 65.3%, and 100% for high-intensity statin, high-intensity statin plus ezetimibe, and triple therapy, respectively (Figure 1). Baseline LDL-C category analysis revealed that patients with baseline LDL-C ≥160 mg/dL required triple therapy to reach guideline targets, while those with baseline LDL-C <100 mg/dL achieved targets with high-intensity statin monotherapy. Conclusions High-intensity statin monotherapy is insufficient for most ACS patients to achieve ESC/EAS LDL-C targets. To bridge the gap between guidelines and clinical practice, early initiation of combination therapy is essential, particularly for patients with baseline LDL-C 160 mg/dL who necessitate a "triple therapy" approach from the outset.