PCSK9 inhibitors in the prevention of cardiovascular disease

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• 作者：James Latimer ; Jonathan A. Batty…
• 关键词：Low ; density lipoprotein ; Proprotein convertase subtilisin kexin type 9 (PCSK9) ; Prevention ; Monoclonal antibody ; Evolocumab ; Alirocumab
• 刊名：Journal of Thrombosis and Thrombolysis
• 出版年：2016
• 出版时间：October 2016
• 年：2016
• 卷：42
• 期：3
• 页码：405-419
• 全文大小：905 KB
• 刊物类别：Medicine
• 刊物主题：Medicine & Public Health
  Cardiology
  Hematology
  
• 出版者：Springer Netherlands
• ISSN：1573-742X
• 卷排序：42

文摘

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.