Beyond expectations: who achieves the greatest LDL-c decline?

Introduction Lipid-lowering therapy is key for reducing cardiovascular risk, but responses to statins and ezetimibe vary widely. Identifying baseline factors that predict LDL-c reduction, including "super-responder" status, may help personalize treatment and optimize outcomes. Purpose The aim of this study was to identify clinical and biochemical predictors of LDL-c response to lipid-lowering therapy. Methods Prospective observational single-center study of lipid lowering therapy-naïve patients admitted to the Cardiology Department with acute coronary syndrome between 2023 and 2025 and subsequently enrolled in a cardiac rehabilitation program. Clinical and laboratory data were collected at admission and post-rehabilitation. Patients were classified as responders if they achieved the average LDL-C percentage reduction reported in the newest ESC guidelines (±10%), and as super-responders if they exceeded it by at least 10%. Results Of the 105 patients enrolled (mean age of 59.3±10.88years), the majority were male (78.1%) and had single-vessel disease (57.3%), 56.2% had hypertension, 55.2% dyslipidemia, 13.3% diabetes and 63.8% had smoking history. Mean LDL-c at admission was 118.6 ± 46.2 mg/dL. At discharge, 5 patients received moderate-intensity statins, 80 received high-intensity statins, 1 received moderate-intensity statin plus ezetimibe, and 19 received high-intensity statin plus ezetimibe. Overall, 64 patients were classified as responders and 31 as super-responders. In univariate analyses, responders had significantly higher admission LDL-c (135.6±46.9 vs 92.1±29.9mg/dL, p<0.001) and higher glomerular filtration rates (eGFR; 86.7±21.3 vs 77.6±20.9, p 0.033), while non-responders had significantly higher Apolipoprotein B levels (ApoB; 77.9±18.0 vs 64.8±19.3, p 0.007) and slightly higher Lipoprotein (a), although not statistically significant (124.8±99.0 vs 83.7±84.7, p 0.063). In multivariate analysis, only admission LDL-c (HR 1.07; p < 0.001) and ApoB (HR 0.89; p = 0.002) remained independently associated with response. Super-responders, in univariate analysis, had higher LDL-c at admission (140.9±53.8 vs 109.3±39.4, p 0.001), lower ApoB (60.7±17.5 vs 74.7±19.3, p 0.005) and higher IPAQ scores (681.9±768.2 vs 360.6±502.8, p 0.049). On multivariate logistic regression, only admission LDL-c (HR 1.02; p = 0.008) and ApoB (HR 0.94; p = 0.009) remained significant. Conclusions Baseline LDL-c and ApoB levels emerged as the strongest predictors of LDL-c reduction following lipid-lowering therapy. Identifying patients with high LDL-c and low ApoB at admission may assist clinicians in anticipating treatment response and optimizing early lipid-lowering strategies.