IMR Press / RCM / Volume 15 / Issue 4 / DOI: 10.3909/ricm0773
Open Access Review
The Potential Role of Anti-PCSK9 Monoclonal Antibodies in the Management of Hypercholesterolemia
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1 The David Geffen School of Medicine at UCLA and Cedars-Sinai Medical Center, Los Angeles, CA
2 Westside Medical Associates of Los Angeles, Beverly Hills, CA
3 The Christ Hospital Heart and Vascular Center, The Lindner Research Center, Cincinnati, OH
Rev. Cardiovasc. Med. 2014 , 15(4), 290–309; https://doi.org/10.3909/ricm0773
Published: 30 December 2014
Abstract
Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of death and disability in developed nations, and it is rising rapidly in other parts of the developing world. Levels of low-density lipoprotein cholesterol (LDL-C) are directly correlated with atherogenic risk, and statin-based therapy is the most common management for these patients. However, many patients exhibit resistance to and/or adverse effects from statin therapy, and there is a need for adjunctive therapies or statin alternatives for these patients. The recently discovered human protein proprotein convertase subtilisin/kexin type 9 (PCSK9) plays an important role in LDL-C metabolism. PCSK9 promotes LDL receptor (LDL-R) degradation with a consequent reduction in LDL-R density and an increase in LDL-C levels. Consequently, PCSK9 inhibition to reduce LDL-C levels has become a primary focus for drug development. Numerous clinical trials focusing on monoclonal antibodies against PCSK9 have demonstrated efficacy equal to or greater than statin therapy for lowering LDL-C levels. Long-term trials are underway to assess safety, tolerability, and ability to reduce ASCVD.
Keywords
Hypercholesterolemia
PCSK9
Low-density lipoprotein cholesterol
Atherosclerotic cardiovascular disease
Anti-PCSK9 monoclonal antibodies
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