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ArtikelReducing LDL with PCSK9 Inhibitors — The Clinical Benefit of Lipid Drugs  
Oleh: Everett, Brendan M. ; Smith, Robert J. ; Hiatt, William R.
Jenis: Article from Journal - ilmiah internasional
Dalam koleksi: The New England Journal of Medicine (keterangan: ada di Proquest) vol. 373 no. 17 (Oct. 2015), page 1588-1591.
  • Perpustakaan FK
    • Nomor Panggil: N08.K
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Isi artikelIn early June, the Endocrinologic and Metabolic Drugs Advisory Committee of the Food and Drug Administration (FDA), on which we serve, met to consider marketing applications for the new molecular entities alirocumab and evolocumab on the basis of their ability to lower low-density lipoprotein (LDL) cholesterol levels and their effects on other lipid fractions in patients at risk for cardiovascular disease. These first-in-class medications are fully humanized monoclonal antibodies that inactivate proprotein convertase subtilisin–kexin type 9 (PCSK9). That inactivation results in decreased LDL-receptor degradation, increased recirculation of the receptor to the surface of hepatocytes, and consequent lowering of LDL cholesterol levels in the bloodstream. Statins, by inhibiting 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, similarly act by increasing LDL-receptor expression. This shared LDL cholesterol–lowering mechanism, combined with data on cardiovascular events from genetic studies of persons with PCSK9 gain- or loss-of-function mutations, has led to optimism regarding the potential — but as yet unproven — cardiovascular benefits of these agents.
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