PCSK9 inhibitors: current status and emerging frontiers in lipid control

Federica Agnello, Maria Sara Mauro, Carla Rochira, Davide Landolina, Simone Finocchiaro, Antonio Greco, Nicola Ammirabile, Carmelo Raffo, Placido Maria Mazzone, Marco Spagnolo, Giovanni Occhipinti, Antonino Imbesi, Daniele Giacoppo, Davide Capodanno

Research output: Contribution to journalReview articlepeer-review

4 Scopus citations

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.

Original languageEnglish
Pages (from-to)41-58
Number of pages18
JournalExpert Review of Cardiovascular Therapy
Volume22
Issue number1-3
DOIs
StatePublished - 2024
Externally publishedYes

Keywords

  • LDL cholesterol
  • PCSK9 inhibitors
  • alirocumab
  • evolocumab
  • inclisiran
  • lipid-lowering therapy

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