Potential Cardiovascular Events Avoided with Bempedoic Acid Plus Ezetimibe Fixed-Dose Combination Compared with Ezetimibe Alone in Patients with Atherosclerotic Cardiovascular Disease Taking Maximally Tolerated Statins

Abstract

Background: Patients with atherosclerotic cardiovascular disease who require additional low-density lipoprotein cholesterol (LDL-C) lowering despite maximally tolerated statins have a significant unmet medical need and are at increased risk of future cardiovascular events and a reduced quality of life.

Objective: We aimed to estimate the percentage of cardiovascular events avoided following treatment with a fixed-dose combination of bempedoic acid plus ezetimibe (BA+EZE FDC) versus ezetimibe (EZE) in patients with atherosclerotic cardiovascular disease receiving maximally tolerated statins across a range of baseline LDL-C levels.

Methods: A Markov cohort simulation model estimated major adverse cardiovascular events avoided over a lifetime horizon among patients with atherosclerotic cardiovascular disease and baseline LDL-C levels from 80 to >200 mg/dL. BA+EZE FDC was compared with EZE based on mean percent LDL-C reductions versus placebo reported in a phase III trial. Health outcomes for the average patient were extrapolated to a US population of 100,000 persons using evidence on contemporary LDL-C levels from the National Health and Nutrition Examination Survey.

Results: Among patients with atherosclerotic cardiovascular disease not at the LDL-C goal with maximally tolerated statins, the addition of BA+EZE FDC compared with the addition of EZE was predicted to provide incremental absolute reductions in major adverse cardiovascular events dependent on baseline LDL-C levels at the population level. For those with baseline LDL-C of 101-110 mg/dL (n = 15,237), there were 4.9% (744) fewer events predicted, while for patients with baseline LDL-C of > 200 mg/dL (n = 1689), 10.9% (184) fewer events were predicted through the addition of BA+EZE FDC versus EZE.

Conclusions: Further LDL-C reductions through the addition of BA+EZE FDC to maximally tolerated statins are predicted to reduce major adverse cardiovascular events compared with the addition of EZE. Benefits are potentially greater among those with higher starting LDL-C.

Fig. 1

Modeling framework for atherosclerotic cardiovascular disease (CVD) progression. A cohort of patients with a high CVD risk (due to atherosclerotic CVD) begins treatment with ezetimibe or bempedoic acid plus ezetimibe fixed-dose combination and may stay in that state, or pass into event states such as myocardial infarction (MI), non-fatal stroke, coronary revascularization, and cardiovascular (CV) death. From there, patients may move into post-event health states where they may have a higher likelihood for additional events or death as compared with a general CVD risk. Death may occur from all-cause or event/post-event-specific mortality

Fig. 2

Lifetime major adverse cardiovascular events (MACE) avoided with bempedoic acid plus ezetimibe fixed-dose combination (BA+EZE FDC) versus EZE. As the 10-year risk increases, driven largely by low-density lipoprotein cholesterol (LDL-C) at baseline, the incremental benefits in terms of 4-point MACE increase. CV cardiovascular, NHANES National Health and Nutrition Examination Survey