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

Study: LDL cholesterol goal 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 category 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 achieve clinically really helpful LDL-C treatment targets.

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

In the present study, scientists conducted a simulation of treatment with two lipid-lowering drugs, including ezetimibe and bempedoic acid, in statin-intolerant patients who’re at a high or very high risk of cardiovascular complications. The first outcomes of the study were LDL-C reduction and LDL-C goal 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. Amongst this subset of patients, 11,286 met the literature-informed definitions of statin intolerance and were included within the simulation study.

The treatment simulation with ezetimibe and bempedoic acid was applied sequentially to the goal patients with statin intolerance. The primary round of treatment simulation with ezetimibe was applied to patients who didn’t meet the really helpful LDL-C goal levels and weren’t 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 couldn’t achieve the goal LDL-C levels after the primary round of treatment with ezetimibe. A Monte Carlo approach was used to estimate LDL-C reductions and LDL-C goal attainment.

Vital observations

A better occurrence of statin intolerance was observed amongst very high cardiovascular-risk patients as in comparison with that amongst high cardiovascular-risk patients. Hypertension was essentially the most common cardiovascular risk think about all the 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. Lower than 10% of patients were receiving ezetimibe monotherapy or statin-ezetimibe combination therapy, whereas about 19% of patients weren’t receiving any lipid-lowering treatments at baseline.  

Simulation of treatment with ezetimibe and bempedoic acid   

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

Considering all the study population with statin intolerance, 7.7% achieved the goal 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 goal LDL-C attainment was higher amongst patients with high cardiovascular risk as in comparison with 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 present simulation study finds that a mixture 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 power of patients to realize clinically relevant LDL-C targets.

It’s well-documented that each ezetimibe and bempedoic acid don’t cause muscle symptoms, that are essentially the most common complications amongst statin-intolerant patients. Furthermore, each drugs are related to low rates of potential treatment contraindications, resembling liver disease and gout. Thus, this mixture therapy might be effectively and safely applied to patients with statin intolerance.