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Targeting the peptidase PCSK9 to reduce cardiovascular risk: Implications for basic science and upcoming challenges
Toshiyuki Nishikido1,2, Kausik K Ray1
1Imperial Centre for Cardiovascular Disease Prevention (ICCP), Department of Primary Care and Public Health, School of Public Health, Imperial College London, London, UK.
Insights
PCSK9 inhibitors offer an alternative for patients unable to achieve LDL cholesterol reduction with statins. These therapies significantly lower LDL-C, reducing cardiovascular risk, especially in high-risk individuals.
Area of Science:
- Cardiology
- Pharmacology
Background:
- Low-density lipoprotein cholesterol (LDL-C) is a key factor in atherosclerosis development.
- Statins are the primary treatment for high LDL-C, but some patients have inadequate response or intolerance.
- PCSK9 inhibitors represent an alternative therapeutic strategy for LDL-C reduction.
Purpose of the Study:
- To review PCSK9-targeted therapies for managing LDL-C.
- To discuss the challenges and benefits of LDL-C reduction in preventing atherosclerotic cardiovascular disease.
Main Methods:
- Review of current literature on PCSK9 inhibitors.
- Analysis of the role of LDL-C reduction in cardiovascular risk.
- Discussion of therapeutic strategies and patient stratification.
Main Results:
- PCSK9 monoclonal antibodies significantly reduce LDL-C levels and cardiovascular risk.
- Newer PCSK9 inhibitors with novel mechanisms are under development.
- The benefit of LDL-C reduction is proportional to baseline risk and achieved reduction.
Conclusions:
- PCSK9 inhibitors are effective alternatives for statin-refractory or intolerant patients.
- Targeting PCSK9 offers significant cardiovascular risk reduction, particularly for high-risk populations.
- Optimizing LDL-C reduction strategies is crucial for atherosclerotic cardiovascular disease prevention.
Abstract:
LDL cholesterol (LDL-C) plays a central role in the progression of atherosclerosis. Statin therapy for lowering LDL-C reduces the risk of atherosclerotic cardiovascular disease and is the recommended first-line treatment for patients with high LDL-C levels. However, some patients are unable to achieve an adequate reduction in LDL-C with statins or are statin-intolerant; thus, PCSK9 inhibitors were developed to reduce LDL-C levels, instead of statin therapy. PCSK9 monoclonal antibodies dramatically reduce LDL-C levels and cardiovascular risk, and promising new PCSK9 inhibitors using different mechanisms are currently being developed. The absolute benefit of LDL-C reduction depends on the individual absolute risk and the achieved absolute reduction in LDL-C. Therefore, PCSK9 inhibitors may provide the greatest benefits from further LDL-C reduction for the highest risk patients. Here, we focus on PCSK9-targeted therapies and discuss the challenges of LDL-C reduction for prevention of atherosclerotic cardiovascular disease.
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