Treatment intensification with bempedoic acid to achieve LDL-C goal in patients with ASCVD: A simulation model using a real-world patient cohort in the US

Abstract

Background and aims: Guidelines recommend that high-risk patients with atherosclerotic cardiovascular disease (ASCVD) be treated with maximally tolerated statins to lower low-density lipoprotein cholesterol (LDL-C) levels and reduce the risk of major adverse cardiovascular events. In patients whose LDL-C remains elevated, non-statin adjunct therapies, including ezetimibe (EZE), bempedoic acid (BA), and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors are recommended.

Methods: The impact of BA and EZE in a fixed-dose combination (FDC) on LDL-C goal attainment was evaluated using a simulation model developed for a United States cohort of high-risk adults with ASCVD. Treatment was simulated for 73,056 patients not at goal (LDL-C >70 mg/dL), comparing BA + EZE (FDC), EZE only, and no oral adjunct therapy (NOAT). The addition of PCSK9 inibitors was assumed after 1 year in patients not at LDL-C goal. Treatment efficacy was estimated from clinical trials. Patient-level outcomes were predicted over a 10-year horizon accounting for treatment discontinuation and general mortality.

Results: Baseline mean age of the cohort was 67 years, most were White (79%) and male (56%). A majority had established coronary artery disease (75%), 48% had diabetes, and mean LDL-C was 103.0 mg/dL. After 1 year, 79% of patients achieved LDL-C goal (mean, 61.1 mg/dL) with BA + EZE (FDC) compared to 58% and 42% with EZE (71.7 mg/dL) and NOAT (78.4 mg/dL), respectively.

Conclusions: This simulation shows that adding BA + EZE (FDC) to maximally tolerated statins would result in more patients achieving LDL-C goal than adding EZE alone or NOAT.

Graphical abstract

Fig. 1

Model structure. LDL-C goal was <70 mg/dL in base case; <55 mg/dL explored in scenario analysis. Dashed lines were 50% in base case, and 0% or 100% in scenarios. BA = bempedoic acid; EZE = ezetimibe; FDC = fixed-dose combination; LDL-C = low density lipoprotein cholesterol; MACE = major adverse cardiovascular event; PCSK9i = proprotein convertase subtilisin/kexin type 9 inhibitor.

Fig. 2

Proportion of patients in the overall population predicted to reach LDL-C goal at year 1 with and without PCSK9 inhibitor. Values may not add up to the total values due to rounding. BA = bempedoic acid; EZE = ezetimibe; FDC = fixed-dose combination; LDL-C, low-density lipoprotein cholesterol; NOAT = no oral adjunct therapy; PCSK9 = proprotein convertase subtilisin/kexin type 9.

Fig. 3

Predicted LDL-C levels at year 1, by treatment pathway. LDL-C levels at year 1 for patients recieving (A) BA + EZE (FDC) (n = 71,645), (B) EZE (n = 71,737), and (C) NOAT (n = 71,587). Percentages may not add up to 100% due to rounding. The total number of patients included in each analysis represents the number of patients simulated to be alive at year 1. BA = bempedoic acid; EZE = ezetimibe; FDC = fixed-dose combination; LDL-C = low density lipoprotein cholesterol; NOAT = no oral adjunct therapy.