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Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitors: A Novel Approach in Hypercholesterolemia Management: A Review of Phase-III Clinical Trials

Marco Bustamante Bernal, Mohamed Teleb, Syed H. Saad, Miraie Wardi, Carlos Rodriguez

Department of Internal Medicine, Texas Tech University Health Sciences Center, El Paso, TX, USA

Med Sci Rev 2015; 2:8-14

DOI: 10.12659/MSRev.893611

Available online:

Published: 2015-02-16


Abstract: Despite optimum statin therapy, the treatment of hypercholesterolemia faces challenges such as the failure to reach low LDL cholesterol (LDL-C) levels and intolerability that lead to discontinuation of therapy. Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors have emerged as a potential solution to further decrease LDL-C levels and consequently reduce cardiovascular risk.
PCSK9 plays a major role in regulating levels of LDL-C by binding to hepatic receptors and promoting their degradation. The inhibition of PCSK9 reduces the degradation of LDL-C receptors and also reduces triglycerides and other lipoproteins.
Clinical trials have shown promising results in lipid-lowering therapy with the use the PCSK9 inhibitors alirocumab, Evolocumab, and bococizumab, either as mono therapy or in combination with statins in different patient populations. Results for Evolocumab in phase II trials showed a reduction of LDL-C from 41% to 66%. The present review focuses on phase III clinical trials because phase I and II trials provided a promising future approach that might effectively treat one of the leading causes of cardiovascular disease.

Keywords: Cholesterol, LDL, Hypercholesterolemia, Proprotein Convertases