LDL-cholesterol goal attainment with ezetimibe and bempedoic acid in patients at high and very-high cardiovascular risk: A simulation study in the Italian cohort of the SANTORINI study

Aims: Data from the Italian cohort of the SANTORINI study, a European observational study focusing on lipid management in patients at high or very-high cardiovascular risk, were used to simulate the effect of sequential addition of ezetimibe and bempedoic acid in patients not at LDL-C goal with their current lipid-lowering therapy (LLT). Methods: Eligible patients were selected based on criteria including LDL-C levels and LLT status. Patients who were not at LDL-C goal at baseline and had not received PCSK9 inhibitors (PCSK9i) or bempedoic acid underwent sequentially 1) simulation of adding ezetimibe in patients who had not previously received this drug, and 2) simulation of the effect of adding bempedoic acid in patients who did not achieve the LDL-C goal after treatment with ezetimibe (actual or simulated). Expected treatment efficacy was documented from randomised clinical trials. The simulation assumed no statin intensification beyond the baseline regimen. The simulation was run probabilistically 10,000 times for the patient cohort, calculating the mean LDL-C after each simulation step and estimating the proportion of patients achieving LDL-C goal at each stage and overall. Results: The simulation resulted in a significant increase in patients achieving the LDL-C goal after each step (from 25.9% to 37.6% after ezetimibe and 55.4% after ezetimibe+bempedoic acid). The subgroup analysis showed similar trends in high-risk and very-high-risk patients. Conclusions: The simulation of SANTORINI data shows that goal attainment in patients at high-risk and very-high-risk can be substantially increased by optimizing oral LLT with the addition of ezetimibe and bempedoic acid. This is the update version of the article. A correction has been published: EAJ 2024;3:93 - https://doi:10.56095/eaj.v3i3.86