Expert consensus on the rational clinical use of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors.

Dimitrios Tousoulis, George Ntaios, Nikolaos Papanas, Stavros Pappas, Christos Pitsavos, Loukianos Rallidis, Dimitrios Richter, Ioannis Skoumas, Nicolaos Tentolouris, Vasilios Nikolaou, Alexandros Tselepis, Konstantinos Tsioufis, Dimitrios Tziakas, Konstantinos Tziomalos, Panagiotis Vardas, Charalabos Vlachopoulos, Dimitrios Vlahakos, Emanouel Ganotakis, Theodoros Alexandrides, Dimitrios Alexopoulos, Vasilios Athyros, Alexandra Bargiota, Eleni Bilianou, Christina Chrysochoou, Evridiki Drogari, Moses Elisaf, Apostolos Achimastos, Ioannis Goudevenos, Ioannis Ioannidis, Genovefa Kolovou, Vasilios Kotsis, Ioannis Lekakis, Evangelos Liberopoulos, Andreas Melidonis

Journal: Hormones (Athens, Greece) 2017;15(1):8-14

PMID: 27086681

Free Full Text on Hormones View on PubMed

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.

Address: Professor of Internal Medicine, Medical School, National and Kapodistrian University of Athens, Athens, Greece.; Professor of Internal Medicine-Endocrinology, Medical School, University of Patras, Patras, Greece.; Professor of Cardiology, Medical School, University of Patras, Patras, Greece.; Associate Professor of Internal Medicine, Past President of the Hellenic Atherosclerosis Society Aristotle University of Thessaloniki, Thessaloniki, Greece.; Assistant Professor of Internal Medicine-Endocrinology, Medical School, University of Thessaly, Larissa, Greece.; Consultant-Cardiology, Head of Lipid Outpatient Clinic, "Tzaneio" General Hospital of Piraeus, Piraeus, Greece.; Consultant Cardiology, 1st University Cardiology Clinic, "Hippokratio" General Hospital of Athens, Athens, Greece.; Assistant Professor of Metabolic Pediatrics, Medical School, National and Kapodistrian University of Athens, Athens, Greece.; Professor of Internal Medicine, Medical School, Past President of the Hellenic Atherosclerosis Society, University of Ioannina, Ioannina, Greece.; Professor of Internal Medicine, Medical School, Past President of the Hellenic Atherosclerosis Society, University of Crete, Heraklion, Greece.; Professor of Cardiology, Medical School, University of Ioannina, Ioannina, Greece.; Consultant-Internal Medicine, Head of the Diabetes and Obesity Outpatient Clinics, General Hospital of Nea Ionia "Konstantopouleio-Patission", Athens, Greece.; 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.; Assistant Professor of Internal Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece.; Professor of Cardiology, Medical School, National and Kapodistrian University of Athens, Athens, Greece.; Assistant Professor of Internal Medicine, Medical School, University of Ioannina, Ioannina, Greece.; Consultant-Internal Medicine, Coordinator-Director of 1st Internal Medicine Clinic, "Tzaneio" General Hospital of Piraeus, Pireaus, Greece.; Consultant-Cardiology, "Korgialenio Benakio" "HRC" Hospital, Athens, Athens, Greece.; Assistant Professor of Internal Medicine, Medical School, University of Thessaly, Larissa, Greece.; Associate Professor of Internal Medicine, Medical School, Democritus University of Thrace, Alexandroupolis, Greece.; Internist-Diabetologist, President of the Institute for the Study, Research and Training on Diabetes Mellitus and Metabolic Diseases, Athens, Athens, Greece.; Emeritus Professor of Cardiology, Medical School, National and Kapodistrian University of Athens, Athens, Greece.; Associate Professor of Cardiology, Medical School, University of Athens, Athens, Greece.; Director of Cardiology Department, Athens Euroclinic, President of the Hellenic Society of Lipidology and Atherosclerosis, Athens, Athens, Greece.; Cosultant-Cardiology, Head of the Lipid Unit of the 1st University Clinic, "Hippokratio" General Hospital of Athens, Athens, Greece.; Associate Professor of Internal Medicine, Medical School, National and Kapodistrian University of Athens, Athens, Greece.; Professor of Biochemistry-Clinical Chemistry, President of the Hellenic Atherosclerosis Society, University of Ioannina, Ioannina, Greece.; Associate Professor of Cardiology, National and Kapodistrian University of Athens, Athens, Greece.; Professor of Cardiology, Medical School, Democritus University of Thrace, Alexandroupolis, Greece.; Assistant Professor of Medicine, Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece.; Professor of Cardiology, Medical School, Past President of the European Cardiology Society, University of Crete, Heraklion, Greece.; Associate Professor of Cardiology, President of the European Society of Cardiology working Group for Peripheral Circulation, National and Kapodistrian University of Athens, Athens, Greece.; Associate Professor of Nephrology, National and Kapodistrian University of Athens, Athens, Greece.

DOI: 10.14310/horm.2002.1659