Use of bempedoic acid in an out-patient setting: an assessment of efficacy heterogeneity

Objectives We describe decreases in total cholesterol (TC), non-high density lipoprotein-cholesterol (non-HDL-C) and low density lipoprotein-cholesterol (LDL-C) following bempedoic acid treatment in an out-patient setting and compare the results to those observed in phase 3 efficacy trials. Methods We analysed a cohort of 113 patients not achieving LDL-C targets commenced on bempedoic acid after previous treatment with statins and ezetimibe using an intention-to-treat approach. We compared pre and post bempedoic acid treatment lipids (3-months) in the total cohort using paired t-tests. Baseline patient characteristics associated with LDL-C decrease was established via linear/multiple regression analyses. Results Following bempedoic acid treatment absolute reduction (mean ± SD) in TC, non-HDL-C, and LDL-C values were 1.1 ± 1.0mmol/L, 1.0 ± 1.0mmol/L, and 1.0 ± 0.9mmol/L, respectively, whilst percentage reductions (mean ± SD) were 16.4 ± 14.1%, 18.8 ± 17.2%, and 23.2 ± 20.5%, respectively. Significant decreases in the lipids were observed in every subgroup studied. The LDL-C decrease following bempedoic acid was independently greater in ex-smokers, individuals on ezetimibe at baseline, and those with higher baseline LDL-C values. Conclusions Our results show that the LDL-C decrease seen with bempedoic acid was comparable to that observed in the phase 3 efficacy trials. However, efficacy heterogeneity was observed in some of the subgroups studied such as patients on ezetimibe monotherapy or with higher LDL-C at baseline, the latter in accordance with the Wilder principle. The use of effect scores for identified patient subgroups might predict treatment response, enabling optimisation of lipid lowering efficacy.