• Norman E Lepor, Laurn Contreras, Chirag Desai, and Dean J Kereiakes.
• The David Geffen School of Medicine at UCLA and Cedars-Sinai Medical Center, Los Angeles, CA; Westside Medical Associates of Los Angeles, Beverly Hills, CA.
• Rev Cardiovasc Med. 2014 Jan 1; 15 (4): 290-307; quiz 308-9.

AbstractAtherosclerotic 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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