Related Experiment Video
Updated: Mar 22, 2026
A High-Throughput Luciferase Assay to Evaluate Proteolysis of the Single-Turnover Protease PCSK9
Published on: August 28, 2018
PCSK9 inhibitors in the prevention of cardiovascular disease
James Latimer1, Jonathan A Batty1,2, R Dermot G Neely1,3
1Institute of Cellular Medicine, Faculty of Medical Sciences, Newcastle University, M3.131, 3rd Floor William Leech Building, Newcastle upon Tyne, NE2 4HH, UK.
Abstract:
Reducing plasma levels of low-density lipoprotein cholesterol (LDL-C) remains the cornerstone in the primary and secondary prevention of cardiovascular disease. However, lack of efficacy and adverse effects mean that a substantial proportion of patients fail to achieve acceptable LDL-C levels with currently available lipid-lowering drugs. Over the last decade, inhibition of proprotein convertase subtilisin/kexin type 9 (PCSK9) has emerged as a promising therapeutic strategy to reduce residual cardiovascular disease risk. Binding of PCSK9 to the LDL receptor targets the receptor for lysosomal degradation. The recognition that inhibition of PCSK9 increases LDL receptor activity has led to the development of a number of approaches to directly target PCSK9. Numerous monoclonal antibodies against PCSK9 are currently being evaluated in phase 3 trials, involving various patient categories on different background lipid-lowering therapies. Current evidence shows reductions in LDL-C levels of up to 70 % may be achieved with PCSK9 inhibition, independent of background statin therapy. This review examines the most recent evidence and future prospects for the use of PCSK9 inhibitors in the prevention of cardiovascular disease.
Insights
PCSK9 inhibitors offer a novel approach to lower LDL-C, significantly reducing cardiovascular disease risk. These treatments achieve substantial LDL-C reductions, independent of statins, for patients unresponsive to current therapies.
Area of Science:
- Cardiovascular Medicine
- Pharmacology
- Biochemistry
Background:
- Lowering low-density lipoprotein cholesterol (LDL-C) is crucial for cardiovascular disease (CVD) prevention.
- Many patients do not achieve target LDL-C levels with existing lipid-lowering drugs due to efficacy limitations and adverse effects.
- Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibition has emerged as a key strategy to address residual CVD risk.
Purpose of the Study:
- To review the latest evidence on PCSK9 inhibitors for cardiovascular disease prevention.
- To explore the therapeutic potential and future prospects of targeting PCSK9.
- To highlight the mechanism of PCSK9 inhibition and its impact on LDL receptor activity.
Main Methods:
- Review of current phase 3 clinical trial data for PCSK9 inhibitors.
- Analysis of the mechanism of PCSK9 binding to LDL receptors and subsequent degradation.
- Evaluation of LDL-C reduction efficacy across diverse patient populations and background therapies.
Main Results:
- PCSK9 inhibition can achieve up to 70% reduction in LDL-C levels.
- Efficacy of PCSK9 inhibition is independent of background statin therapy.
- Monoclonal antibodies targeting PCSK9 are in late-stage clinical trials for various patient groups.
Conclusions:
- PCSK9 inhibition represents a significant advancement in lipid-lowering therapy.
- This approach offers a promising strategy for managing residual cardiovascular risk.
- Further research and clinical application of PCSK9 inhibitors are anticipated for CVD prevention.
Related Concept Videos
01:29Pharmacogenomics: Identification of New Drug Targets
01:26Coronary Artery Disease IV: Preventive Measures
01:20Lipid-Lowering Drugs: Statins and Miscellaneous Agents
01:20Antiplatelet Drugs: Prostaglandin Synthesis, P2Y12 and Glycoprotein IIb/IIIa Inhibitors
Prostaglandin synthesis inhibitors, exemplified by the widely known aspirin, wield their power by irreversibly acetylating...
01:26Atherosclerosis III: Management
01:27Coronary Artery Disease V: Interprofessional Care