AI Article Synopsis

  • Atherosclerotic cardiovascular disease (ASCVD) is a major global health issue, significantly driven by high levels of LDL cholesterol; new therapies like PCSK9 inhibitors aim to reduce this risk.
  • The article discusses how PCSK9 regulates LDL receptors and reviews various ways to inhibit it, demonstrating that these new treatments can effectively lower LDL cholesterol levels and improve heart health based on trial results.
  • Although monoclonal antibodies are a key focus among PCSK9 inhibitors and show promising benefits, challenges such as their high cost, long-term safety, and who should receive them require ongoing investigation.

Article Abstract

Introduction: Atherosclerotic cardiovascular disease (ASCVD) is a leading cause of global mortality, imposing substantial healthcare economic burdens. Among the modifiable risk factors, hypercholesterolemia, especially elevated low-density lipoprotein cholesterol (LDL-C), plays a pivotal role in ASCVD development. Novel therapies such as PCSK9 (Proprotein Convertase Subtilisin/Kexin type 9) inhibitors are emerging to address this concern. These inhibitors offer the potential to reduce ASCVD risk by directly targeting LDL-C levels.

Areas Covered: The article reviews the structural and functional aspects of PCSK9, highlighting its role in LDL receptor regulation. The pharmacological strategies for PCSK9 inhibition, including monoclonal antibodies, binding peptides, gene silencing, and active immunization, are explored. Clinical evidence from various trials underscores the safety and efficacy of PCSK9 inhibitors in reducing LDL-C levels and potentially improving cardiovascular outcomes. Despite these promising results, challenges such as cost-effectiveness and long-term safety considerations are addressed.

Expert Opinion: Among PCSK9 inhibitors, monoclonal antibodies represent a cornerstone. Many trials have showed their efficacy in reducing LDL-C and the risk for major adverse clinical events, revealing long-lasting effects, with special benefits particularly for statin-intolerant and familial hypercholesterolemia patients. However, long-term impacts, high costs, and patient selection necessitate further research.

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Source
http://dx.doi.org/10.1080/14779072.2023.2288169DOI Listing

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