Early intensive combination lipid-lowering therapy in statin-naïve acute coronary syndrome: real-world attainment of lipid targets and analysis of therapeutic gaps

Background Achieving the low-density lipoprotein cholesterol (LDL-C) targets recommended by the ESC/EAS guidelines remains challenging in routine practice for very-high-risk patients. Purpose We aimed to evaluate LDL-C target attainment following inpatient initiation of intensive combination lipid-lowering therapy in statin-naïve acute coronary syndrome (ACS) patients and to explore factors associated with successful attainment. Methods In this prospective single-center cohort study, we enrolled statin-naïve ACS patients undergoing coronary revascularization. All patients were prescribed high-intensity combination therapy (rosuvastatin 20 mg or atorvastatin 40 mg plus ezetimibe 10 mg daily) at discharge. The primary endpoint was the proportion of patients achieving LDL-C <1.4 mmol/L at 1 and 6 months. For patients not achieving the target, the therapeutic gap (absolute distance to target and percentage reduction required) was analyzed. Multivariable logistic regression was performed to identify factors associated with goal attainment. Safety outcomes were also assessed. Results A total of 277 patients were recruited. Mean LDL-C levels decreased from 2.56 mmol/L at baseline to 1.06 mmol/L at 1 month and 1.08 mmol/L at 6 months. LDL-C target attainment rates (<1.4 mmol/L) were 83.8% and 83.4%, respectively. Among the 45 non-attainers at 6 months, 35.6% had a residual therapeutic gap >0.5 mmol/L, and only 5 patients (11.1% of non-attainers; 1.8% of total cohort) required >50% additional LDL-C reduction. (Figure 1) Higher baseline LDL-C was associated with lower goal attainment at 6 months (OR 0.60, p=0.004). Additionally, good medication adherence was significantly associated with 6-month goal attainment (OR 4.97, p = 0.007) (Table 1). Combination therapy was safe and well-tolerated. Elevated liver enzymes or treatment discontinuation due to possible adverse reactions occurred in only 1.35% of patients. Conclusions Inpatient initiation of high-intensity statin plus ezetimibe enabled over 80% of statin-naïve ACS patients to achieve stringent ESC/EAS LDL-C targets with an acceptable safety profile. Most non-attainers were close to the target, and medication adherence emerged as a critical determinant of goal attainment. Patients with very high baseline LDL-C may require closer monitoring or consideration of additional therapies to close the residual therapeutic gap.