https://doi.org/10.1007/s00392-024-02526-y
1University of Cologne Center for Endocrinology, Diabetes and Preventive Medicine Cologne, Deutschland; 2Leiden University Medical Center Department of Cardiology Leiden, Niederlande; 3Bern University Hospital Department of Cardiology Bern, Schweiz; 4Imperial College London Imperial Centre for Cardiovascular Disease Prevention, ICTU-Global London, Großbritannien; 5University of Palermo Department ProMISE – Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties Palermo, Italien; 6Clinic Hietzing Department of Medicine III and Karl Landsteiner Institute for Metabolic Diseases and Nephrology Vienna, Österreich; 7University Hospitals Leuven Department of Cardiovascular Medicine Leuven, Belgien; 8Daiichi Sankyo Europe GmbH Munich, Deutschland; 9Hospital Universitari de Bellvitge-Idibell-UB-CiberObn Department of Internal Medicine Barcelona, Spanien; 10Ludwig-Maximilians University Munich LMU-Klinikum Medical Department 4 Munich, Deutschland
Background: Bempedoic acid (BA), a first-in-class adenosine triphosphate-citrate lyase inhibitor, has demonstrated reductions in low-density lipoprotein cholesterol (LDL-C) levels and risk of cardiovascular (CV) events in randomised trials. 1,2 However, data on BA in clinical practice are limited. MILOS is a prospective, observational European study (NCT04579367) evaluating BA and the BA + ezetimibe (EZE) fixed-dose combination (FDC) in adults with primary hypercholesterolaemia or mixed dyslipidaemia. We report final 2-year (Y) follow-up data from the German cohort of the MILOS Study.
Methods: Patients were recruited in Germany between January 2021–January 2022, and followed for 2 years after baseline measurements. Change in LDL-C levels and the proportion of patients achieving LDL-C goal were assessed in patients at pre-treatment, 1Y and 2Y visits. Adverse drug reactions (ADRs) were assessed through 2Y.
Results: The mean (standard deviation [SD]) age of 973 patients enrolled in 126 sites in Germany was 64.9 (10.0) years; 61.9% (n=602) were male (Table). Overall, 65.6% (638/973) of patients completed 2Y follow-up (mean [SD]: 725.5 [46.0] days). Of these, 70.7% (451/638) had LDL-C data for pre-treatment, 1Y and 2Y visits; baseline characteristics were similar to the overall population (Table). Before initiation of BA or the BA + EZE FDC, 34.5% (336/973) of patients had no documented background use of lipid-lowering therapies (LLTs). At 2Y follow-up, BA or the BA + EZE FDC was used without other LLTs by 26.3% (256/973) of enrolled patients and in combination with other LLTs by 38.1% (371/973). From pre-treatment to 2Y after study inclusion, mean (SD) LDL-C decreased from 3.14 (1.25) mmol/L to 2.00 (0.90) mmol/L (from 121.4 [48.4] mg/dL to 77.2 [34.7] mg/dL), representing a mean (SD) relative LDL-C reduction of 30.3% (35.8). The proportion of patients achieving LDL-C goals increased from 4.9% (22/451) at pre-treatment to 35.3% (159/451) at 2Y; similar results were seen in both high- and very high-CV risk patients (Figure). Throughout the 2Y follow-up, 16.2% (158/973) of patients had an ADR considered by the investigator to be related to BA or the BA + EZE FDC (107/973 [11.0%]), or with unknown causality (51 /973 [5.2%]); 0.5% (5/973) of patients had serious ADRs considered related (3/973 [0.3%]), or with unknown causality (2/973 [0.2%]).
Conclusions: The use of BA alone or the BA + EZE FDC, with or without other LLTs, was associated with an almost one-third relative reduction in LDL-C from pre-treatment to 2Y, and a greater than 7-fold increase in the proportion of patients achieving their LDL-C goal. The safety profile of BA in this real-world population was consistent with that observed in clinical trials.
2. Nissen SE, et al. J Chem 2020; 388:1353–64