HYPERLIPIDEMIA AND CARDIOVASCULAR DISEASE: Edited by Paul N. DurringtonEvidence for improved survival with treatment of homozygous familial hypercholesterolemiaBélanger, Alexandre M.a; Akioyamen, Leob; Alothman, Latifaha; Genest, JacquesaAuthor Information aResearch Institute of the McGill University Health Centre, Royal Victoria Hospital, Montreal, Quebec bFaculty of Medicine, University of Toronto, Toronto, Ontario, Canada Correspondence to Professor Jacques Genest, MD, FRCP(C), FAHA, Professor, Faculty of Medicine, McGill University, Novartis Chair in Medicine at McGill, McGill University Health Center/Royal Victoria Hospital, 1001, boul. Décarie, Bloc E, Office EM12212 Montréal, QC H4A 3J1, Canada. Tel: +1 514 934 1934, 34642; e-mail: email@example.com Current Opinion in Lipidology: August 2020 - Volume 31 - Issue 4 - p 176-181 doi: 10.1097/MOL.0000000000000686 Buy Metrics Abstract Purpose of review Homozygous familial hypercholesterolemia (HoFH) is an orphan disease caused by biallelic mutations at the LDL receptor (LDLR) gene, with a prevalence estimated at 1 : 250 000 to 1 : 630 000. HoFH is characterized by extremely elevated plasma levels of LDL-C greater than 10 mmol/l (>387 mg/dl), tendinous and cutaneous xanthomas in youth and premature atherosclerotic cardiovascular disease (ASCVD). The expected prevalence varies from country to country depending on the presence of founder effects, genetic probability and life expectancy. Untreated, HoFH is a fatal condition before age 30. Plasma levels of LDL-C are the major cause of mortality and the therapeutic target. Statin therapy led to a remarkable improvement in survival but is of limited use in loss-of-function LDLR gene variants or ‘null’ mutations. Inhibitors of PCSK9 are a useful adjunct in patients with LDLR mutations with residual activity. Extracorporeal LDL filtration has improved survival since its introduction three decades ago. Recent findings Novel therapies, not dependent on a functioning LDLR include lomitapide and mipomersen, which decrease hepatic apolipoprotein B secretion, and evinacumab, directed at the angiopoietin like-3 protein (ANGPLT-3). Summary Over the past 3–4 decades, the survival of patients with HoFH has increased markedly. New therapeutic options offer new hope. Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.