Combining ezetimibe and bempedoic acid effectively lowers cholesterol in statin-intolerant patients

By Dr. Sanchari Sinha Dutta, Ph.D.Jan 7 2024Reviewed by Benedette Cuffari, M.Sc.

A recent simulation study published in the journal Scientific Reports analyzed representative data of over two million outpatients in Germany, in which the researchers reported that a combination of lipid-lowering therapy with ezetimibe and bempedoic acid is capable of effectively reducing low-density lipoprotein cholesterol (LDL-C) levels to clinically-recommended levels in statin-intolerant patients with hypercholesterolemia.

Study: LDL cholesterol target attainment in cardiovascular high- and very-high-risk patients with statin intolerance: a simulation study. Image Credit: george martin studio / Shutterstock.com

Background

Statins are a class of lipid-lowering drugs that effectively reduce blood LDL-C levels and improve cardiovascular health in patients with hypercholesterolemia. Intolerance of patients to sufficient doses of statins significantly contributes to their inability to reach clinically recommended LDL-C treatment targets.

Previous studies have indicated that statin intolerance is associated with poor treatment adherence and worse cardiovascular outcomes. In most patients with statin intolerance, muscle pain is the most prominent treatment-related symptom, with the prevalence of these statin-associated muscle symptoms ranging between 7-29%.

In the current study, scientists conducted a simulation of treatment with two lipid-lowering drugs, including ezetimibe and bempedoic acid, in statin-intolerant patients who are at a high or very high risk of cardiovascular complications. The primary outcomes of the study were LDL-C reduction and LDL-C target attainment.

Study design

The study population included 2.06 million German outpatients, 130,778 of whom were identified to be diagnosed with hypercholesterolemia, have high or very-high cardiovascular risk, and available LDL-C results. Among this subset of patients, 11,286 met the literature-informed definitions of statin intolerance and were included in the simulation study.

The treatment simulation with ezetimibe and bempedoic acid was applied sequentially to the target patients with statin intolerance. The first round of treatment simulation with ezetimibe was applied to patients who did not meet the recommended LDL-C target levels and were not receiving ezetimibe at baseline.

The second round of treatment simulation with bempedoic acid was applied to patients who were already receiving ezetimibe at baseline or could not achieve the target LDL-C levels after the first round of treatment with ezetimibe. A Monte Carlo approach was used to estimate LDL-C reductions and LDL-C target attainment.

Important observations

A higher occurrence of statin intolerance was observed among very high cardiovascular-risk patients as compared to that among high cardiovascular-risk patients. Hypertension was the most common cardiovascular risk factor in the entire study population. The mean baseline LDL-C level was 103.6 mg/dL.

About 71% of patients were receiving moderate-intensity statin monotherapy at baseline. Less than 10% of patients were receiving ezetimibe monotherapy or statin-ezetimibe combination therapy, whereas about 19% of patients were not receiving any lipid-lowering treatments at baseline.  

Simulation of treatment with ezetimibe and bempedoic acid   

Among patients who underwent the first round of treatment simulation with ezetimibe, 20.1% achieved the target LDL-C levels. Similarly, about 39% of patients who underwent the second round of treatment simulation with bempedoic acid achieved the target LDL-C levels.

Considering the entire study population with statin intolerance, 7.7% achieved the target LDL-C levels at baseline. This percentage increased to 22.6% and 52% after treatment simulation with ezetimibe and bempedoic acid, respectively.

The prevalence of target LDL-C attainment was higher among patients with high cardiovascular risk as compared to patients with very high cardiovascular risk. The mean LDL-C level of 103.6 mg/dL was reduced to 80 mg/dL and 62 mg/dL after the treatment simulation with ezetimibe and bempedoic acid, respectively. This corresponded to relative reductions of 20% and 38% from baseline, respectively.

Study significance

The current simulation study finds that a combination lipid-lowering treatment with ezetimibe and bempedoic acid has the potential to significantly reduce blood LDL-C levels in statin-intolerant patients, thereby supporting the ability of patients to achieve clinically relevant LDL-C targets.

It is well-documented that both ezetimibe and bempedoic acid do not cause muscle symptoms, which are the most common complications among statin-intolerant patients. Moreover, both drugs are associated with low rates of potential treatment contraindications, such as liver disease and gout. Thus, this combination therapy can be effectively and safely applied to patients with statin intolerance.