Background <p>Intensive low-density lipoprotein cholesterol (LDL-C) lowering after acute coronary syndrome (ACS) is recommended to reduce cardiovascular risk, but real-world attainment of LDL-C targets remains suboptimal. Therapeutic inertia and varying lipid-lowering strategies may contribute to this gap, but their longitudinal impact is not well characterized.</p> Methods <p>In this retrospective longitudinal study, ACS patients with repeated follow-up visits (6–54 months) were evaluated. Lipid-lowering treatment strategies were categorized as no change/discontinuation, combination therapy, dose up-titration, or switching/intensification. A lagged decision–outcome design linked treatment strategies at Visit T_n to LDL-C target attainment at T_<i>n</i>+1. Generalized estimating equations and mixed-effects logistic regression models were used to assess associations with subsequent LDL-C target attainment using the 2016 guideline (&lt; 1.8 mmol/L). For sensitivity analyses, the 2023 guideline was applied (&lt; 1.4 mmol/L).</p> Results <p>A total of 1,731 ACS patients were included, with follow-up visits at 6–54 months. Combination therapy was the most frequently used strategy, followed by dose up-titration and switching/intensification. Notably, 10–15% of visits had no treatment adjustment. Treatment modification was significantly associated with improved LDL-C target attainment. Combination therapy showed the strongest effect (OR 0.25, 95% CI: 0.21–0.30), followed by dose up-titration (OR 0.48, 95% CI: 0.40–0.58) and switching/intensification (OR 0.71, 95% CI: 0.59–0.86). Therapeutic inertia was linked to more than double the risk of persistent LDL-C non-attainment (OR 2.46, 95% CI: 2.09–2.90).</p> Conclusions <p>In ACS patients, lipid-lowering treatment modification, particularly combination therapy, was associated with improved LDL-C target attainment, whereas therapeutic inertia was detrimental. Proactive treatment adjustment is crucial for improving secondary prevention in real-world practice.</p>