Bempedoic acid for LDL-cholesterol management in patients with and without diabetes: insights from the MILOS study

Background Bempedoic acid (BA), a first-in-class adenosine triphosphate-citrate lyase inhibitor, reduces low-density lipoprotein cholesterol (LDL-C), and the risk of cardiovascular (CV) events in randomised trials.1-6 CLEAR Outcomes demonstrated CV risk reduction with BA in patients with diabetes7, however, real-world evidence on its LDL-C lowering effects and goal attainment in this patient population remains limited. Purpose To evaluate effectiveness of BA or BA + ezetimibe fixed dose combination (BA/FDC) in patients with or without diabetes across 5 EU countries (Austria, Belgium, Germany, Italy, and United Kingdom) in the real-world MILOS study data. Methods MILOS (NCT04579367) is a prospective European observational study assessing BA/FDC effectiveness and safety in patients with hypercholesterolemia or mixed dyslipidaemia. Patients were stratified by glycaemic status: diabetes, prediabetes, or normoglycemia. LDL-C data before initiation of BA/FDC and at 1-year follow-up (1Y) after enrolment were analysed. Results Pooled data from 3138 patients (Austria, n=200; Belgium, n=395; Germany, n=973; Italy, n=1331; UK, n=239) were analysed. Of these, 20.6% had diabetes, 18.0% had pre-diabetes, 58.5% had normoglycemia and 2.9% had missing diabetes status. Most patients were male (59.3%) and those with diabetes more commonly had higher BMI (>30 kg/m2) versus other two groups. Investigators classified patients mostly as high and very-high CV risk: diabetes (25.0% and 65.5%), prediabetes (29.1% and 56.7%) and normoglycemia (29.8% and 53.9%), respectively (Table). At BA/FDC initiation, 18.2% received BA monotherapy (diabetes: 20.1%; prediabetes: 15.1%, normoglycemia: 18.4%), and 81.8% received BA in combination therapy (diabetes: 79.9%; prediabetes: 84.9%, normoglycemia: 81.6%; Table). LDL-C values before BA/FDC initiation and at 1 year were available for 2071 patients (18.6% diabetes, 19.9% prediabetes, 59.4% normoglycemia and 2.1% with missing diabetes status). Mean±SD LDL-C levels before initiation of BA/FDC were lower in patients with diabetes vs. prediabetes and normoglycemia (106.6±42.7 vs 118.9±51.1 and 117.3±48.7 mg/dL, respectively). At 1Y follow-up, mean±SD LDL-C for patients with diabetes, prediabetes and normoglycemia were reduced to 74.1±34.7, 76.6±34.9, and 77.3±34.6 mg/dL, corresponding to a mean relative change of -24.9%, -28.7% and -28.2%, respectively (Figure). LDL-C goal attainment from before treatment initiation to 1Y increased across all groups (diabetes: 7.0% to 38.0%; prediabetes: 7.0% to 39.4%, normoglycemia: 7.7% to 37.9%). No new safety signals were observed across the glycaemic subgroups. Conclusions One-year real-world data from the MILOS study show that adding BA/FDC, with or without other lipid lowering treatments, was associated with >24% mean relative LDL-C reduction and an increase in the proportion of patients achieving their LDL-C goal within 1 year, regardless of their diabetes status.