Potential impact on cholesterol goal achievement and predicted cardiovascular risk by the addition of ezetimibe and bempedoic acid on top of statins: a simulation from the SANTORINI study

Background: In SANTORINI, one-third of patients achieved low-density lipoprotein cholesterol (LDL-C) goals at 1-year follow-up, with oral combination therapies used in approximately 38 %. We simulated the potential impact of adding oral lipid-lowering therapies (LLTs) on goal attainment and predicted residual cardiovascular (CV) risk. Methods: Using observed LLT use and LDL-C levels as a baseline, a Monte Carlo simulation was applied. The predicted improvements in LDL-C through the sequential addition of ezetimibe (if not already received) and bempedoic acid (if not at goal with ezetimibe) was evaluated in patients not at goal (LDL-C simulation set; N = 6866), nor receiving background bempedoic acid or proprotein convertase subtilisin/kexin type 9 inhibitor therapies (treatment optimisation set; N = 4467). Predicted 10-year CV risk reduction from expected LDL-C changes were also assessed (CV risk simulation set; N = 4327). Results: Adding ezetimibe and ezetimibe plus bempedoic acid increased the predicted number of patients at goal from 28.4 % to 43.8 % and 63.1 %, respectively. The predicted relative risk reductions of a major CV event was 7.6 % and 13.4 % after each treatment optimisation step. Relative to the predicted residual 10-year risk of 25.1 % at the end of SANTORINI, further LLT optimisation was predicted to lower absolute CV risk by 2.0 % and 3.4 % with each additional LLT optimisation step. Conclusions: Approximately two-thirds of patients could reach their LDL-C targets after the stepwise addition of ezetimibe and bempedoic acid in patients not at goal with statins and/or ezetimibe, with likely meaningful CV risk reductions over 10 years. Funding: This study was funded by Daiichi Sankyo Europe GmbH, Munich, Germany. Trial registration: ClinicalTrials.gov