title: Expert consensus on the rational clinical use of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors.
abstract: Two proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, evolocumab and alirocumab, have recently been approved by both the Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for the treatment of hypercholesterolemia. These fully human monoclonal antibodies selectively block PCSK9, thus permitting the low-density lipoprotein (LDL) receptor to effectively recycle to the surface of liver cells. The administration of these antibodies leads to robust LDL cholesterol (LDL-C) lowering by 50-60% on top of maximum hypolipidemic treatment. At least 4 randomized, placebo-controlled studies are under way and will address the question of whether the administration of these PCSK9 inhibitors is associated with a significant reduction of cardiovascular events. Because of the high cost associated with the use of these medications it is very important to consider which patients may gain the most benefit, at least until the results of outcome studies are available. In this Consensus paper, 34 clinicians/scientists define 3 groups of patients that should be currently considered as candidates for the use of these novel drugs. These include: 1a. Adults with established cardiovascular disease and LDL-C≥100 mg/dL while on lifestyle modifications and maximally tolerated hypolipidemic treatment, i.e. high-intensity statin + ezetimibe, 1b. Adults with diabetes and established cardiovascular disease or chronic kidney disease or target organ damage and LDL-C ≥100 mg/dL while on lifestyle modifications and maximally tolerated hypolipidemic treatment, i.e. high-intensity statin + ezetimibe, 2. Adults with familial hypercholesterolemia (FH) without established cardiovascular disease and LDL-C ≥130 mg/dL while on lifestyle modifications and maximally tolerated hypolipidemic treatment, i.e. high-intensity statin + ezetimibe (evolocumab is also indicated in children above 12 years with homozygous FH), and 3. Adults at high or very high cardiovascular risk who are statin intolerant and have an LDL-C ≥100 and ≥130 mg/dL, respectively, while on any tolerated hypolipidemic treatment.
authors.affiliation: Professor of Internal Medicine, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
authors.forename: Apostolos
authors.initials: A
authors.lastname: Achimastos
authors.affiliation: Professor of Internal Medicine-Endocrinology, Medical School, University of Patras, Patras, Greece.
authors.forename: Theodoros
authors.initials: T
authors.lastname: Alexandrides
authors.affiliation: Professor of Cardiology, Medical School, University of Patras, Patras, Greece.
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Alexopoulos
authors.affiliation: Associate Professor of Internal Medicine, Past President of the Hellenic Atherosclerosis Society Aristotle University of Thessaloniki, Thessaloniki, Greece.
authors.forename: Vasilios
authors.initials: V
authors.lastname: Athyros
authors.affiliation: Assistant Professor of Internal Medicine-Endocrinology, Medical School, University of Thessaly, Larissa, Greece.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Bargiota
authors.affiliation: Consultant-Cardiology, Head of Lipid Outpatient Clinic, "Tzaneio" General Hospital of Piraeus, Piraeus, Greece.
authors.forename: Eleni
authors.initials: E
authors.lastname: Bilianou
authors.affiliation: Consultant Cardiology, 1st University Cardiology Clinic, "Hippokratio" General Hospital of Athens, Athens, Greece.
authors.forename: Christina
authors.initials: C
authors.lastname: Chrysochoou
authors.affiliation: Assistant Professor of Metabolic Pediatrics, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
authors.forename: Evridiki
authors.initials: E
authors.lastname: Drogari
authors.affiliation: Professor of Internal Medicine, Medical School, Past President of the Hellenic Atherosclerosis Society, University of Ioannina, Ioannina, Greece.
authors.forename: Moses
authors.initials: M
authors.lastname: Elisaf
authors.affiliation: Professor of Internal Medicine, Medical School, Past President of the Hellenic Atherosclerosis Society, University of Crete, Heraklion, Greece.
authors.forename: Emanouel
authors.initials: E
authors.lastname: Ganotakis
authors.affiliation: Professor of Cardiology, Medical School, University of Ioannina, Ioannina, Greece.
authors.forename: Ioannis
authors.initials: I
authors.lastname: Goudevenos
authors.affiliation: Consultant-Internal Medicine, Head of the Diabetes and Obesity Outpatient Clinics, General Hospital of Nea Ionia "Konstantopouleio-Patission", Athens, Greece.
authors.forename: Ioannis
authors.initials: I
authors.lastname: Ioannidis
authors.affiliation: Consultant-Cardiology, Head of LDL Apheresis Unit and Lipid Outpatient Clinics, Past President of the Hellenic Atherosclerosis Society, President of the Hellenic College of Treatment of Atherosclerosis, Onassis Cardiac Surgery Center, Athens, Greece.
authors.forename: Genovefa
authors.initials: G
authors.lastname: Kolovou
authors.affiliation: Assistant Professor of Internal Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece.
authors.forename: Vasilios
authors.initials: V
authors.lastname: Kotsis
authors.affiliation: Professor of Cardiology, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
authors.forename: Ioannis
authors.initials: I
authors.lastname: Lekakis
authors.affiliation: Assistant Professor of Internal Medicine, Medical School, University of Ioannina, Ioannina, Greece.
authors.forename: Evangelos
authors.initials: E
authors.lastname: Liberopoulos
authors.affiliation: Consultant-Internal Medicine, Coordinator-Director of 1st Internal Medicine Clinic, "Tzaneio" General Hospital of Piraeus, Pireaus, Greece.
authors.forename: Andreas
authors.initials: A
authors.lastname: Melidonis
authors.affiliation: Consultant-Cardiology, "Korgialenio Benakio" "HRC" Hospital, Athens, Athens, Greece.
authors.forename: Vasilios
authors.initials: V
authors.lastname: Nikolaou
authors.affiliation: Assistant Professor of Internal Medicine, Medical School, University of Thessaly, Larissa, Greece.
authors.forename: George
authors.initials: G
authors.lastname: Ntaios
authors.affiliation: Associate Professor of Internal Medicine, Medical School, Democritus University of Thrace, Alexandroupolis, Greece.
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Papanas
authors.affiliation: Internist-Diabetologist, President of the Institute for the Study, Research and Training on Diabetes Mellitus and Metabolic Diseases, Athens, Athens, Greece.
authors.forename: Stavros
authors.initials: S
authors.lastname: Pappas
authors.affiliation: Emeritus Professor of Cardiology, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
authors.forename: Christos
authors.initials: C
authors.lastname: Pitsavos
authors.affiliation: Associate Professor of Cardiology, Medical School, University of Athens, Athens, Greece.
authors.forename: Loukianos
authors.initials: L
authors.lastname: Rallidis
authors.affiliation: Director of Cardiology Department, Athens Euroclinic, President of the Hellenic Society of Lipidology and Atherosclerosis, Athens, Athens, Greece.
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Richter
authors.affiliation: Cosultant-Cardiology, Head of the Lipid Unit of the 1st University Clinic, "Hippokratio" General Hospital of Athens, Athens, Greece.
authors.forename: Ioannis
authors.initials: I
authors.lastname: Skoumas
authors.affiliation: Associate Professor of Internal Medicine, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
authors.forename: Nicolaos
authors.initials: N
authors.lastname: Tentolouris
authors.affiliation: Professor of Cardiology, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Tousoulis
authors.affiliation: Professor of Biochemistry-Clinical Chemistry, President of the Hellenic Atherosclerosis Society, University of Ioannina, Ioannina, Greece.
authors.forename: Alexandros
authors.initials: A
authors.lastname: Tselepis
authors.affiliation: Associate Professor of Cardiology, National and Kapodistrian University of Athens, Athens, Greece.
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Tsioufis
authors.affiliation: Professor of Cardiology, Medical School, Democritus University of Thrace, Alexandroupolis, Greece.
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Tziakas
authors.affiliation: Assistant Professor of Medicine, Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece.
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Tziomalos
authors.affiliation: Professor of Cardiology, Medical School, Past President of the European Cardiology Society, University of Crete, Heraklion, Greece.
authors.forename: Panagiotis
authors.initials: P
authors.lastname: Vardas
authors.affiliation: Associate Professor of Cardiology, President of the European Society of Cardiology working Group for Peripheral Circulation, National and Kapodistrian University of Athens, Athens, Greece.
authors.forename: Charalabos
authors.initials: C
authors.lastname: Vlachopoulos
authors.affiliation: Associate Professor of Nephrology, National and Kapodistrian University of Athens, Athens, Greece.
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Vlahakos
mesh_terms: D006801:Humans; D006937:Hypercholesterolemia / Q000188:drug therapy; D000960:Hypolipidemic Agents / Q000627:therapeutic use; D000091362:PCSK9 Inhibitors; D000071449:Proprotein Convertase 9
chemical_list: D000960:Hypolipidemic Agents; D000091362:PCSK9 Inhibitors; C472125:PCSK9 protein, human; D000071449:Proprotein Convertase 9