Adding Ezetimibe to High-Intensity Statin at the Time of Admission in Patients With Acute Coronary Syndrome: Results From the Optimization of Low-Density Lipoprotein Cholesterol After Acute Coronary Syndrome (OLA) Study

Achieving rapid and substantial reductions in low-density lipoprotein cholesterol (LDL-C) soon after acute coronary syndrome (ACS) is associated with improved cardiovascular outcomes. Current guidelines recommend high-intensity statin therapy, yet many patients fail to reach LDL-C targets early, putting them at continued risk. The present study investigates whether upfront combination therapy with rosuvastatin 40 mg and ezetimibe 10 mg, started at admission, is more effective and efficient in achieving early LDL-C goals compared to statin monotherapy in statin-naïve ACS patients. In this single-center prospective study, statin-naïve patients presenting with ACS and undergoing percutaneous coronary intervention were started on combination therapy (rosuvastatin 40 mg plus ezetimibe 10 mg, n=63). Lipids were measured at baseline and one, two, four, and six weeks. Results were compared to a retrospective, matched cohort (n=61) treated with rosuvastatin 40 mg monotherapy, who had complete baseline and week 4 lipid profiles. The primary endpoint was the percent LDL-C reduction at four weeks post-ACS and the proportion of patients achieving LDL-C targets of <50 mg/dl and <70 mg/dl by four weeks. Secondary endpoints included kinetics of LDL-C lowering, safety, and tolerability. Baseline LDL-C was similar between groups (115.2 ± 29.3 vs. 118.8 ± 35.4 mg/dl, p=0.65). At four weeks, mean LDL-C was 43.4 ± 12.2 mg/dl (combination) and 65.3 ± 25.3 mg/dl (monotherapy), signifying reductions of 62.3% and 45.1%, respectively (p=0.04). LDL-C targets of <50 mg/dl and <70 mg/dl were achieved at substantially higher rates in the combination group (74.6% vs. 27.9% and 95.2% vs. 59.1%, respectively; both p<0.0001). Maximal LDL-C reduction occurred within two weeks and persisted to six weeks. Combination therapy was safe and well-tolerated, with only mild myalgias observed in 19% of patients, none requiring treatment cessation. Upfront initiation of rosuvastatin plus ezetimibe in ACS achieves rapid, profound, and sustained LDL-C lowering, with significantly higher rates of target attainment than high-intensity statin monotherapy. Early combination therapy represents an accessible, pragmatic, and cost-effective strategy for high-risk patients, especially in resource-limited environments.