caa a22 4500 606158480 CHVBK 20210128100619.0 cr unu---uuuuu 210128e20150601xx s 000 0 eng 10.1007/s10557-015-6588-3 doi (NATIONALLICENCE)springer-10.1007/s10557-015-6588-3 PCSK9 Inhibition: Discovery, Current Evidence, and Potential Effects on LDL-C and Lp(a) [Elektronische Daten] [Keith Ferdinand, Samar Nasser] Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a serine protease that binds to low-density lipoprotein receptors (LDL-Rs), leading to their accelerated degradation and increased low-density lipoprotein cholesterol (LDL-C) levels. Therefore, PCSK9 levels play a critical role in cholesterol metabolism by reducing LDL-R levels and thus increasing levels of plasma LDL-C. Recently, investigational agents inhibiting PCSK9 have been shown to lower LDL-C and also, potentially, an important secondary target, lipoprotein(a). Therefore, several pharmaceutical companies have initiated drug-development programs that target PCSK9 and are built on a solid foundation of basic science, genetic studies, and epidemiological observations. PCSK9 inhibition with monoclonal antibodies demonstrated LDL-C lowering of up to 57% when the PCSK9 antibodies are used as monotherapy and up to 73% when added to background lipid-lowering therapy. In addition, long-term cardiovascular outcome studies are currently under way to confirm the longer term safety and efficacy of PCSK9 inhibitors and to determine whether PCSK9 inhibition lowers the incidence of major cardiovascular events. PCSK9 inhibitors may provide safe and effective lipid-lowering therapy, especially for patients with inadequate LDL-C lowering on lipid-lowering treatments, those who are statin intolerant or have contraindications to statin therapy, and those with hereditary hypercholesterolemia/familial hypercholesterolemia and severely elevated LDL-C. Springer Science+Business Media New York, 2015 Alirocumab nationallicence Evolocumab nationallicence Hypercholesterolemia nationallicence Lipoprotein(a) nationallicence Low-density lipoprotein cholesterol nationallicence Proprotein convertase subtilisin/kexin type 9 nationallicence Ferdinand Keith Tulane Heart and Vascular Institute, Tulane University School of Medicine, 1430 Tulane Avenue, #8548, 70112, New Orleans, LA, USA aut Nasser Samar Department of Clinical Research and Leadership, School of Medicine and Health Sciences, The George Washington University, 20037, Washington, DC, USA aut Cardiovascular Drugs and Therapy Springer US; http://www.springer-ny.com 29/3(2015-06-01), 295-308 0920-3206 29:3<295 2015 29 10557 https://doi.org/10.1007/s10557-015-6588-3 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s10557-015-6588-3 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Ferdinand Keith Tulane Heart and Vascular Institute, Tulane University School of Medicine, 1430 Tulane Avenue, #8548, 70112, New Orleans, LA, USA aut NATIONALLICENCE 700 1- Nasser Samar Department of Clinical Research and Leadership, School of Medicine and Health Sciences, The George Washington University, 20037, Washington, DC, USA aut NATIONALLICENCE 773 0- Cardiovascular Drugs and Therapy Springer US; http://www.springer-ny.com 29/3(2015-06-01), 295-308 0920-3206 29:3<295 2015 29 10557