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Updated: Aug 20, 2025

A High-Throughput Luciferase Assay to Evaluate Proteolysis of the Single-Turnover Protease PCSK9
Published on: August 28, 2018
Safety of PCSK9 inhibitors
Grzegorz Grześk1, Bednarska Dorota1, Łukasz Wołowiec1
1Department of Cardiology and Clinical Pharmacology, Faculty of Health Sciences, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University, Toruń, Poland.
Insights
PCSK9 inhibitors offer a new way to lower LDL cholesterol when statins aren't enough. This review summarizes their safety profile to aid therapeutic decisions for cardiovascular disease patients.
Area of Science:
- Cardiovascular Medicine
- Pharmacology
- Biochemistry
Background:
- Cardiovascular diseases, primarily atherosclerosis, cause 4 million deaths annually in Europe.
- Lowering LDL cholesterol (LDL-C) is crucial for managing atherosclerotic plaque development.
- Statins are standard therapy, but only 43% of patients achieve LDL-C targets.
Purpose of the Study:
- To review the safety profile of PCSK9 inhibitors.
- To provide information aiding therapeutic decisions regarding PCSK9 inhibitors.
Main Methods:
- Review of studies on PCSK9 inhibitors (evolocumab, alirocumab, bococizumab, inclisiran).
- Assessment of safety and tolerability data from clinical trials.
- Evaluation of pleiotropic effects, including metabolic and inflammatory impacts.
Main Results:
- PCSK9 inhibitors effectively lower LDL-C levels.
- Monoclonal antibodies and synthesis inhibitors target the PCSK9 protein.
- Pleiotropic effects on metabolism and inflammation have been identified.
Conclusions:
- PCSK9 inhibitors represent a significant advancement in lipid-lowering therapy.
- Understanding their safety profile is essential for clinical application.
- These drugs offer an alternative for patients not reaching LDL-C goals with statins.
Abstract:
annually in Europe, 4 million people die from cardiovascular diseases, the main cause of which is atherosclerosis. In order to slow down the development of atherosclerotic plaques, the main therapeutic goal is to lower LDL cholesterol (LDL-C) level. Undoubtedly, statins are the basis of lipid-lowering therapy for many years. However, a European study shows that only 43% of statin-taking patients achieved their LDL-C targets. PCSK9 inhibitors are a new group of lipid-lowering drugs whose main point of action is the protein discovered in 2003 - the PCSK9 (proprotein convertase subtilisin/kexin 9). This protein is responsible for reducing the density of LDL receptors on the surface of hepatocytes, which increases the value of LDL-C. The discovery of this protein was soon after the basis for the start of research, thanks to which three monoclonal antibodies against PCSK9 were developed - evolocumab, alirocumab, bococizumab - and inclisiran, an inhibitor of PCSK9 synthesis in the liver. In addition to the mechanism of action of PCSK9 inhibitors, resulting in lowering LDL-C level, a number of pleiotropic mechanisms have also been identified, including effects on metabolic processes and inflammation. Until the registration and introduction of above-mentioned drugs into everyday clinical practice, many studies were carried out, in which, in addition to assessing the effectiveness of treatment, the safety and tolerability of the drug were also examined. The purpose of this review is to summarize information on the safety profile of PCSK9 inhibitors, which may help in making therapeutic decision.
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