Lipoprotein apheresis and new therapies for severe familial hypercholesterolemia in adults and children

• Published in: Baillière's best practice & research. Clinical endocrinology & metabolism Vol. 28; no. 3; pp. 387 - 403
• Main Authors: Page, Michael M., BPharm, MBBS (Hons), Bell, Damon A., MB ChB, FRCPA, FRACP, Hooper, Amanda J., BSc (Hons), PhD, Watts, Gerald F., DSc, PhD, MD, FRACP, FRCP, Burnett, John R., MB ChB, MD, PhD, FRCPA
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 01.06.2014
• Subjects: Adult; antisense oligonucleotides; apheresis; apolipoprotein B; Blood Component Removal - adverse effects; Blood Component Removal - methods; Child; cholesteryl ester transfer protein inhibitors; Contraindications; Endocrinology & Metabolism; familial hypercholesterolemia; gene therapy; Humans; Hyperlipoproteinemia Type II - blood; Hyperlipoproteinemia Type II - diagnosis; Hyperlipoproteinemia Type II - epidemiology; Hyperlipoproteinemia Type II - therapy; Lipoproteins - blood; Lipoproteins - isolation & purification; liver transplantation; low density lipoprotein cholesterol; Mass Screening; microsomal triglyceride transfer protein inhibitors; proprotein convertase subtilisin/kexin type 9 inhibitors; Severity of Illness Index; antisense oligonucleotides; apheresis; familial hypercholesterolemia; microsomal triglyceride transfer protein inhibitors; cholesteryl ester transfer protein inhibitors; proprotein convertase subtilisin/kexin type 9 inhibitors; gene therapy; apolipoprotein B; liver transplantation; low density lipoprotein cholesterol
• ISSN: 1521-690X; 1878-1594
• DOI: 10.1016/j.beem.2013.10.004

Familial hypercholesterolemia (FH), the most common and severe monogenic form of hypercholesterolemia, is an autosomal co-dominant disease characterized by an increased plasma low density lipoprotein (LDL)-cholesterol concentration and premature coronary heart disease (CHD). The clinical phenotype depends on the gene involved and severity of mutation (or mutations) present. Patients with homozygous or compound heterozygous FH have severe hypercholesterolemia (LDL-cholesterol >13 mmol/L) due to a gene dosing effect and without treatment have accelerated atherosclerotic CHD from birth, and frequently die of CHD before age 30. Cholesterol-lowering therapies have been shown to reduce both mortality and major adverse cardiovascular events in individuals with FH. Lipoprotein apheresis concomitant with lipid-lowering therapy is the treatment of choice for homozygous FH. This article describes the rationale and role of lipoprotein apheresis in the treatment of severe FH and outlines the recent advances in new pharmacotherapies for this condition.