4.5 Article

PCSK9 inhibition in patients with hypercholesterolemia

期刊

TRENDS IN CARDIOVASCULAR MEDICINE
卷 25, 期 7, 页码 567-574

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ELSEVIER SCIENCE LONDON
DOI: 10.1016/j.tcm.2015.01.009

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  1. AHRQ [1066474, 5K12HS023000-05] Funding Source: Federal RePORTER
  2. AHRQ HHS [K12 HS023000] Funding Source: Medline

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Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a serine protease that plays an important role in modulating low-density lipoprotein cholesterol (LDL-C) levels by targeting LDL-C receptors for lysosomal degradation. Genetic association studies have demonstrated that loss-of-function mutations in PCSK9 are associated with low plasma LDL-C levels and a reduction in the incidence of adverse cardiovascular events. Monoclonal antibodies directed against PCSK9 have been developed and have been shown in phase 1, 2, and 3 trials to dramatically reduce LDL-C regardless of background lipid-lowering therapy, including in clinically challenging populations such as patients intolerant to statin therapy and those with familial hypercholesterolemia. To date, the clinical trials have not raised any significant safety concerns, with no appreciable excess of myalgias, elevation in aminotransferases, or other adverse events. Large, cardiovascular outcomes trials are underway to assess definitively the efficacy and safety of 3 monoclonal antibodies (evolocumab, alirocumab, and bococizumab), while additional non-monoclonal antibody approaches to inhibit PCSK9 continue in the early-phase development. (C) 2015 Elsevier Inc. All rights reserved.

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