PCSK9 inhibitors in the prevention of cardiovascular disease.
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.
Institute of Cellular Medicine, Faculty of Medical Sciences, Newcastle University, M3.131, 3rd Floor William Leech Building, Newcastle upon Tyne, NE2 4HH, UK.
James
J
Latimer
Institute of Cellular Medicine, Faculty of Medical Sciences, Newcastle University, M3.131, 3rd Floor William Leech Building, Newcastle upon Tyne, NE2 4HH, UK.|Freeman Hospital, Newcastle upon Tyne NHS Foundation Trust, Newcastle upon Tyne, UK.
Jonathan A
JA
Batty
Institute of Cellular Medicine, Faculty of Medical Sciences, Newcastle University, M3.131, 3rd Floor William Leech Building, Newcastle upon Tyne, NE2 4HH, UK.|Royal Victoria Infirmary, Newcastle upon Tyne NHS Foundation Trust, Newcastle upon Tyne, UK.
R Dermot G
RD
Neely
Institute of Cellular Medicine, Faculty of Medical Sciences, Newcastle University, M3.131, 3rd Floor William Leech Building, Newcastle upon Tyne, NE2 4HH, UK. vijay.kunadian@newcastle.ac.uk.|Freeman Hospital, Newcastle upon Tyne NHS Foundation Trust, Newcastle upon Tyne, UK. vijay.kunadian@newcastle.ac.uk.
Vijay
V
Kunadian
D000924:Anticholesteremic Agents; D002318:Cardiovascular Diseases / Q000517:prevention & control*; D008078:Cholesterol, LDL / Q000378:metabolism; D006801:Humans; D000091362:PCSK9 Inhibitors; D011973:Receptors, LDL / Q000378:metabolism; D000071449:Proprotein Convertase 9
D000924:Anticholesteremic Agents; D008078:Cholesterol, LDL; D000091362:PCSK9 Inhibitors; D011973:Receptors, LDL; C573412:LDLR protein, human; C472125:PCSK9 protein, human; D000071449:Proprotein Convertase 9
Alirocumab; Evolocumab; Low-density lipoprotein; Monoclonal antibody; Prevention; Proprotein convertase subtilisin kexin type 9 (PCSK9)