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  • Title: The potential role of anti-PCSK9 monoclonal antibodies in the management of hypercholesterolemia.
    Author: Lepor NE, Contreras L, Desai C, Kereiakes DJ.
    Journal: Rev Cardiovasc Med; 2014; 15(4):290-307; quiz 308-9. PubMed ID: 25662924.
    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.
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