This 8-week randomized controlled trial aims to evaluate the efficacy and safety of a fixed-dose combination of bempedoic acid (180 mg) and ezetimibe (10 mg) compared to atorvastatin dose escalation to 80 mg in patients with uncontrolled LDL cholesterol (LDL-C) despite being on atorvastatin therapy. The study focuses on patients aged 18-80 years who have LDL-C levels more than 55 mg/dL, despite being on atorvastatin 40 mg for at least 6 weeks. The primary hypothesis is that the combination therapy of bempedoic acid and ezetimibe will not be inferior to atorvastatin 40 mg in reducing LDL-C levels.

The trial includes two groups: one receiving the combination of bempedoic acid and ezetimibe with a placebo for atorvastatin, and the other receiving atorvastatin 40 mg with a placebo for the combination therapy. Both groups will be treated for 8 weeks, with follow-up visits at 4 and 8 weeks to monitor LDL-C levels, other lipid parameters (such as total cholesterol, non-HDL-C, lipoprotein (a) and triglycerides), and safety outcomes. The study also evaluates the proportion of patients achieving LDL-C levels below 55 mg/dL and compares the safety profiles of both treatments.

Statistical analysis will include ANCOVA to compare LDL-C changes between the two groups, adjusting for baseline LDL-C levels and other relevant factors. Safety and tolerability will be assessed through the incidence of adverse events, laboratory abnormalities, and any serious adverse events. With an estimated sample size of 60 patients, the study aims to provide insights into the potential of the bempedoic acid and ezetimibe combination as a viable alternative for patients who do not achieve sufficient LDL-C control with atorvastatin.