title: From proprotein convertase subtilisin/kexin type 9 to its inhibition: state-of-the-art and clinical implications.
abstract: Statins are recommended as first-line therapy for patients with hypercholesterolaemia. A sizable proportion of patients, however, does not reach therapeutic goals, is statin intolerant, or, despite optimal statin therapy, is at high risk of ischaemic events. Proprotein convertase subtilisin/kexin type 9 (PCSK9) plays a major role in lipid metabolism and several comorbidities. Monoclonal antibodies targeting PCSK9 are a new lipid-lowering approach with the potential to improve clinical outcomes in patients with dyslipidaemia. In this review, we discuss current experimental and clinical evidence of the role of PCSK9 and its inhibition on lipid metabolism and several pathologic conditions with a focus on clinical outcomes. A state-of-the-art analysis of current clinical evidence and future directions on PCSK9 and its inhibition is provided.
authors.affiliation: Systematic Investigation and Research on Interventions and Outcomes (SIRIO) MEDICINE Research Network, Düsseldorf, Germany Department of Internal Medicine, Division of Cardiology, Pulmonology and Vascular Medicine, Heinrich-Heine-University Düsseldorf, Moorenstr. 5, 40225 Düsseldorf, Germany elianonavarese@gmail.com eliano.navarese@alice.it.
authors.forename: Eliano P
authors.initials: EP
authors.lastname: Navarese
authors.affiliation: Systematic Investigation and Research on Interventions and Outcomes (SIRIO) MEDICINE Research Network, Düsseldorf, Germany Collegium Medicum in Bydgoszcz, University of Nicolaus Copernicus, Toruń, Poland.
authors.forename: Michalina
authors.initials: M
authors.lastname: Kołodziejczak
authors.affiliation: Systematic Investigation and Research on Interventions and Outcomes (SIRIO) MEDICINE Research Network, Düsseldorf, Germany Department of Internal Medicine, Division of Cardiology, Pulmonology and Vascular Medicine, Heinrich-Heine-University Düsseldorf, Moorenstr. 5, 40225 Düsseldorf, Germany.
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Dimitroulis
authors.affiliation: Systematic Investigation and Research on Interventions and Outcomes (SIRIO) MEDICINE Research Network, Düsseldorf, Germany Department of Internal Medicine, Division of Cardiology, Pulmonology and Vascular Medicine, Heinrich-Heine-University Düsseldorf, Moorenstr. 5, 40225 Düsseldorf, Germany.
authors.forename: Georg
authors.initials: G
authors.lastname: Wolff
authors.affiliation: Systematic Investigation and Research on Interventions and Outcomes (SIRIO) MEDICINE Research Network, Düsseldorf, Germany Department of Internal Medicine, Division of Cardiology, Pulmonology and Vascular Medicine, Heinrich-Heine-University Düsseldorf, Moorenstr. 5, 40225 Düsseldorf, Germany.
authors.forename: Hans L
authors.initials: HL
authors.lastname: Busch
authors.affiliation: Systematic Investigation and Research on Interventions and Outcomes (SIRIO) MEDICINE Research Network, Düsseldorf, Germany Department of Emergency and Organ Transplantation (DETO), University of Bari, Bari, Italy.
authors.forename: Fiorella
authors.initials: F
authors.lastname: Devito
authors.affiliation: Intensive Cardiac Care Unit, Cardiology Department, Hospital de la Santa Creu I Sant Pau, Barcelona, Spain.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Sionis
authors.affiliation: Systematic Investigation and Research on Interventions and Outcomes (SIRIO) MEDICINE Research Network, Düsseldorf, Germany Department of Emergency and Organ Transplantation (DETO), University of Bari, Bari, Italy.
authors.forename: Marco Matteo
authors.initials: MM
authors.lastname: Ciccone
mesh_terms: D000924:Anticholesteremic Agents / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D000960:Hypolipidemic Agents / Q000627:therapeutic use*; D008077:Lipoproteins, LDL / Q000378:metabolism; D000091362:PCSK9 Inhibitors; D000071449:Proprotein Convertase 9 / Q000378:metabolism*
chemical_list: D000924:Anticholesteremic Agents; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D000960:Hypolipidemic Agents; D008077:Lipoproteins, LDL; D000091362:PCSK9 Inhibitors; C472125:PCSK9 protein, human; D000071449:Proprotein Convertase 9
keywords: Clinical perspectives; PCSK9 inhibitors; Proprotein convertase subtilisin/kexin type 9 (PCSK9)