Prediction of response to bempedoic acid in post-myocardial infarction patients followed in a Cardiac Rehabilitation Program

Background Lipid control is suboptimal in real life after an acute coronary syndrome. Bempedoic acid is a relatively new lipid-lowering therapy (LLT) which inhibits adenosine triphosphate-citrate lyase (ACL) in the liver, acting two steps upstream of hydroxymethylglutaryl-CoA (HMG-CoA) reductase inhibitors (statins). While it could be a useful tool to achieve lipid goals in patients after myocardial infarction (MI) included in a Cardiac Rehabilitation Program (CRP), the response to bempedoic acid in patients treated with high-intensity LLT is uncertain. Purpose We aim to evaluate the effectiveness of bempedoic acid in MI patients included in a CRP and to analyse the predictors of bempedoic acid response. Methods We prospectively included post-MI patients in our local CRP between November 2021 and September 2024. Baseline characteristics, biochemical parameters and pharmacological therapy, including LLT, were recorded. Basal low-density lipoprotein cholesterol (LDL-C) was collected and/or estimated by correcting for previous LLT. Bempedoic acid was targeted mainly to patients with LDL-C between 55 and 70mg/dL despite being treated with high-intensity combined oral LLT. We analysed the difference between measured and theoretical LDL-C (LDL-C before infarction minus theoretical LDL-C reduction by prescribed LLT), which was defined as "residual difference in LDL-C (RD-LDL-C)". The efficacy of bempedoic acid was compared in two subgroups: 1. Positive RD-LDL-C, i.e. lower than theoretically expected, potentially indicating greater margin for intervention in the liver cholesterol synthesis metabolic pathway which includes the ACL and HMG-CoA reductase, and 2. Patients with negative RD-LDL-C, i.e. LDL-C reduction ≥100% than theoretically expected, potentially indicating a more saturated liver cholesterol synthesis metabolic pathway. A p<0.05 was considered statistically significant. Results The entire cohort comprised 290 patients enrolled in our CRP after MI. Bempedoic acid was prescribed to 67 patients (23%). Mean age was 64±11 years, 51 (76%) were male, 61 patients (91%) had a previous diagnosis of hypercholesterolemia, and 13 (19%) had diabetes mellitus. Basal LDL-C before MI was 159±45 mg/dL and LDL-C before bempedoic acid prescription was 68±14 mg/dL. After bempedoic acid prescription, mean LDL-C was 54±24 mg/dL (absolute difference -14±17 mg/dL, relative difference -17±33%). According to initial LLT response, patients with negative RD-LDL-C had lower response to bempedoic acid than patients with positive RD-LDL-C (absolute difference -3±22 mg/dL vs. -19±26 mg/dL, relative difference -4±35% vs. -23±31%, p <0.05 for all comparisons). Conclusions Bempedoic acid exhibits a high variability of response in LDL-C reduction in post-MI patients followed in our CRP. Initial response to high-intensity LLT could be useful in identifying responders and non-responders to bempedoic acid.