Search
- Page Path
- HOME > Search
Review Articles
- Next-generation PCSK9 inhibitors: clinical evidence and future directions for cardiovascular prevention
- Hyun-Jin Kim
- Cardiovasc Prev Pharmacother. 2025;7(4):141-145. Published online October 22, 2025
- DOI: https://doi.org/10.36011/cpp.2025.7.e17
- 6,782 View
- 28 Download
-
Abstract
PDF - Low-density lipoprotein cholesterol (LDL-C) is a causal and modifiable risk factor for atherosclerotic cardiovascular disease, and intensive reduction of LDL-C is central to prevention strategies. Meta-analyses have shown that each 1 mmol/L (approximately 38.7 mg/dL) decrease in LDL-C confers about a 22% relative risk reduction in major vascular events, independent of baseline LDL-C levels. Despite the proven efficacy of statins and ezetimibe, many patients fail to reach recommended LDL-C targets due to inadequate response, intolerance, or poor adherence to daily therapy. The development of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors has transformed lipid management, providing substantial LDL-C reduction. Recently, next-generation agents with extended dosing intervals have emerged, including recaticimab, a fully human monoclonal antibody, and inclisiran, a small interfering RNA therapy. Recaticimab binds circulating PCSK9, preventing degradation of the low-density lipoprotein receptor, and achieves sustained LDL-C reductions of about 50% with dosing every 8 to 12 weeks. Inclisiran employs N-acetylgalactosamine (GalNAc)-mediated hepatocyte delivery to silence PCSK9 messenger RNA, producing comparable LDL-C reductions with twice-yearly maintenance dosing after an initial loading dose. Their extended dosing schedules offer potential benefits in adherence and long-term lipid control, particularly for high-risk patients who struggle with frequent dosing or have statin intolerance. As outcome data accumulate, these therapies may further reduce residual atherosclerotic cardiovascular disease risk and become increasingly important in comprehensive prevention strategies.
- Re-evaluating the PCSK9 guidelines for low-density lipoprotein cholesterol targets: weighing the benefits against the risks
- Terry Gbaa, John Bolodeoku
- Cardiovasc Prev Pharmacother. 2024;6(3):85-91. Published online July 30, 2024
- DOI: https://doi.org/10.36011/cpp.2024.6.e11
- 14,206 View
- 99 Download
-
Abstract
PDF
- Cardiovascular disease management has made significant progress with lipid-lowering interventions, primarily statin therapy. However, statins' side effects, combined with their variable efficacy, have sparked interest in alternative treatments, particularly proprotein convertase subtilisin/kexin type 9 (PCSK9) monoclonal antibodies. These biologics, approved by the US Food and Drug Administration and the European Medicines Agency, have shown a significant impact on lipid levels, particularly low-density lipoprotein cholesterol (LDL-C), resulting in a 50% to 60% reduction. Despite the benefits of PCSK9 inhibitors, the guidelines for their use differ, with specific thresholds determining eligibility. The National Institute for Health and Care Excellence recommends starting PCSK9 therapy for patients with LDL-C levels above 3.5 mmol/L and lipid levels above 5.0 mmol/L who do not have cardiovascular disease. This rigid framework, while cost-effective, may exclude a subset of patients who do not meet these criteria despite having a high cardiovascular risk. The limited scope of these guidelines presents a challenge for specialists managing patients excluded as a result of LDL-C levels that fall just below the threshold but still show signs of significant cardiovascular risk. Recent audits revealed that a significant proportion of patients fall into this grey area, emphasizing the importance of re-evaluating LDL targets for PCSK9 inhibitor initiation. Biological variations, pharmacogenomics, and other factors all contribute to this challenge, highlighting the importance of personalized medicine.
First
Prev
