Ezetimibe Versus Alirocumab and Plaque Vulnerability in Patients with Acute Coronary Syndrome Not Achieving LDL-Cholesterol Target with Statin Therapy: The COMBI-LLT-ACS Randomized Trial

Why clinicians should know about it

• Picked for Cardiology and Cardiovascular Medicine (paper of the day, 19 October 2026): Alirocumab vs ezetimibe on plaque vulnerability in ACS

Abstract

Objective: To compare two lipid-lowering therapy strategies involving Ezetimibe and Alirocumab on the vulnerability of atherosclerotic plaque (AP) in patients with acute coronary syndrome (ACS) not achieving the LDL-cholesterol target while on intensive statin therapy. Methods: Combi-LLT-ACS (Patients receiving combination lipid-lowering therapy admitted with the acute coronary syndrome) included 125 patients aged 59 (51; 64) years, of whom 67.2% were men. All underwent percutaneous coronary intervention of the IRA; also, all patients had at least one stenosis < 50% in non-IRA, had high compliance with statins, and did not reached LDL-C level of ≤1.4 mmol/L. Patients underwent Coronary Computed Tomography Angiography (CCTA) to detect vulnerable AP as well as lipid profile and numerous biomarkers: neutrophil to lymphocyte ratio (NLR), monocyte to lymphocyte ratio (MLR), monocyte to high-density lipoprotein ratio (MHR), systemic inflammatory response index (SIRI), matrix metalloprotease type 9 (MMP-9), tissue inhibitor of metalloproteinases type 1 (TIMP-1), Galectin-3 (GAL-3), neutrophil gelatinase-associated lipocalin (NGAL), and C-reactive protein (CRP). Thereafter, they were randomized into two groups, Ezetimibe vs. Alirocumab, on the same visit. The follow-up period was 52 weeks. We used the following CCTA criteria to detect vulnerable AP: positive remodeling, napkin-ring sign, spotty calcification, and low-attenuation plaque. Results: One month after ACS, vulnerable APs were observed by CCTA in 56 patients (44.8%). After 52 weeks, 10 (17.9%) patients showed stabilization of previously vulnerable APs or a decrease in the number of AP vulnerability criteria. At week 52, TC and LDL-C levels decreased significantly over time in both groups. Both arms of therapy demonstrated a positive effect on the inflammatory markers and markers of extracellular matrix remodeling. Direct comparison of changes between groups revealed no statistically significant differences in the number of vulnerability criteria (p = 0.930); however, in the group receiving Ezetimibe, we found a statistically significant change over the observation period (p = 0.032). Conclusions: Among patients with ACS, receiving a high-intensity statin in combination with Ezetimibe or Alirocumab prevented the emergence of new vulnerable coronary lesions over 52 weeks. While direct regression of specific vulnerability criteria was not observed, these therapeutic strategies were associated with a reduction in LDL-C and biomarkers of inflammation and extracellular matrix remodeling.

Abstract as published, via PubMed.