Simulation of bempedoic acid in the lipid-lowering treatment pathway using the European contemporary SANTORINI cohort of high- and very high-risk patients

Abstract

Abstract Background Lowering LDL-C treatment goals in the 2019 ESC/EAS guidelines necessitates greater use of combination therapies (1). Cost of PCSK9 inhibitors (PCSK9i) and efficacy of ezetimibe alone as add on therapies limit population level achievement of LDL-C goals. Purpose This simulation study assessed the addition of oral bempedoic acid (BA) to ezetimibe in the treatment pathway in a real-world cohort of patients in order to assess the proportion of patients who might reach goal. Methods SANTORINI is a cohort study of European patients at high or very-high CV risk. Patients who were receiving any known LLT regimen with available data on LDL-C at baseline were eligible for this analysis. For patients not at risk-based LDL-C goals, the following treatment algorithm was applied (Figure 1), first the addition of ezetimibe and subsequently BA for those on statins, or addition of BA for those on ezetimibe and not at goal. Patients on PCSK9i remained in the cohort but no simulation was done. LDL-C reductions associated with ezetimibe and BA treatment were based on probabilistic distributions sourced from clinical trial efficacies based on prior studies (2–3). The effect of treatment on LDL-C levels was simulated through a Monte Carlo simulation run 10,000 times. No statin intensification was simulated as we assumed statin therapy was at maximum tolerated dose. Results At baseline (N=6252), mean age was 66 years and mean baseline LDL-C was 80.6 mg/dL with 1444 patients (23%) at goal; 93% (n=5797) were very high risk and 7% (n=455) high risk, of whom 84% (n=5227) were on statins, 23% (n=1447) on ezetimibe and 9% (n=546) on PCSK9i. Out of 4486 patients entering the simulation, 3419 received ezetimibe add-on with a third of those predicted to be achieving their risk-based goal (32%, n=1078/3419). Of those on ezetimibe and not at goal, the addition of BA would be predicted to result in another 36% goal achievement (n=1218/3408). Overall, the number of patients at goal would be expected to increase from 1444 (23%) at baseline to 2522 (40%) and 3740 (60%) after addition of ezetimibe and BA, sequentially. The mean LDL-C for the whole cohort would be expected to fall through this pathway from 80.6 mg/dL at baseline to 69.2 mg/dL and 61.1 mg/dL, respectively. Conclusion Few patients in the SANTORINI cohort were at goal at baseline and few would have LDL-C eligible for PCSK9i use. Optimising use of ezetimibe and BA after statins in the ESC/EAS 2019 LLT pathway could result in significantly more patients attaining lipid goals with likely additional health benefits. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Daiichi Sankyo Europe GmbH