Predicted change in 10-year cardiovascular risk one year after initiation of bempedoic acid-based therapy in the MILOS study
K G Parhofer, M Averna, I Gouni Berthold, J W Jukema, K Koskinas, R Chhabra, O Ajnakina, C Becker, X Pinto, J E R van Lennep, T Stulnig, T Vanassche, K K RayAbstract
Background
In routine clinical practice, many patients remain above their recommended risk-based LDL-C goals for multiple reasons, including but not limited to statin intolerance or LDL-C levels remaining elevated despite statin monotherapy. Several oral non-statin agents are available as adjunctive therapies, including ezetimibe and bempedoic acid. However, the expected impact of LDL-C reductions achieved through optimization of oral lipid-lowering therapy with these agents on long-term cardiovascular (CV) risk in multinational routine-care populations has not yet been quantified.
Purpose
To estimate the expected change in predicted 10-year CV risk associated with LDL-C reductions observed during the first year after initiation of bempedoic acid or its fixed-dose combination with ezetimibe in a multinational European cohort.
Methods
MILOS is a prospective European observational study assessing effectiveness and safety of bempedoic acid or its fixed-dose combination with ezetimibe in adults with primary hypercholesterolaemia or mixed dyslipidaemia managed in routine care. Patients from four European countries (i.e., from Austria, Belgium, Italy, and the United Kingdom) with available LDL-C values before bempedoic acid initiation and at 1-year follow-up after enrolment were included. Ten-year CV risk was estimated using validated prediction models: SCORE2 or SCORE2-OP for individuals without established atherosclerotic cardiovascular disease (ASCVD) and the REACH equation for those with ASCVD. Individual LDL-C changes were translated into relative risk reductions per mmol/L decrease using Cholesterol Treatment Trialists’ methodology. Probabilistic sampling was applied to account for uncertainty, and absolute (ARR) and relative (RRR) risk reductions were summarised.
Results
Among 960 eligible patients, the mean age was 66.8 years, and most were at high or very high CV risk, with clinically manifest ASCVD and elevated LDL-C despite background lipid-lowering therapy (Table). Mean predicted 10-year CV risk was 28.9% before treatment initiation. Mean LDL-C reduction from pre-treatment to 1-year follow-up was 0.88 mmol/L, which corresponds to an estimated ARR of 4.8% in 10-year CV risk (SD 6.7; Figure) or a RRR of 17.1% (SD 20.5). Findings were directionally consistent across countries, with RRR ranging from 14% to 24% and ARR between 4.4% and 5.2%. Patients at higher baseline risk were predicted to benefit more with greater absolute predicted reductions.
Conclusions
This analysis of a multinational real-world cohort suggests that LDL-C reductions in the MILOS study observed 1 year after initiation of bempedoic acid-based therapy would translate into potentially meaningful reductions in predicted 10-year CV risk under sustained LDL-C lowering. These findings complement randomized evidence and illustrate the expected impact of treatment intensification in routine practice with available oral agents.