title: Therapeutic Management of Familial Hypercholesterolemia: Current and Emerging Drug Therapies.
abstract: Familial hypercholesterolemia (FH) is a genetic disorder characterized by significantly elevated low-density lipoprotein cholesterol (LDL-C) concentrations that result from mutations of the LDL receptor, apolipoprotein B (apo B-100), and proprotein convertase subtilisin/kexin type 9 (PCSK9). Early and aggressive treatment can prevent premature atherosclerotic cardiovascular disease in these high-risk patients. Given that the cardiovascular consequences of FH are similar to typical hypercholesterolemia, traditional therapies are utilized to decrease LDL-C levels. Patients with FH should receive statins as first-line treatment; high-potency statins at high doses are often required. Despite the use of statins, additional treatments are often necessary to achieve appropriate LDL-C lowering in this patient population. Novel drug therapies that target the pathophysiologic defects of the condition are continuously emerging. Contemporary therapies including mipomersen (Kynamro, Genzyme), an oligonucleotide inhibitor of apo B-100 synthesis; lomitapide (Juxtapid, Aegerion), a microsomal triglyceride transfer protein inhibitor; and alirocumab (Praluent, Sanofi-Aventis/Regeneron) and evolocumab (Repatha, Amgen), PCSK9 inhibitors, are currently approved by the U.S. Food and Drug Administration for use in FH. This review highlights traditional as well as emerging contemporary therapies with supporting clinical data to evaluate current recommendations and discuss the future direction of FH management.
authors.affiliation: Department of Pharmacy Practice, Thomas Jefferson University, Jefferson College of Pharmacy, Philadelphia, Pennsylvania.
authors.forename: Roshni S
authors.initials: RS
authors.lastname: Patel
authors.affiliation: Department of Pharmacy Practice, Thomas Jefferson University, Jefferson College of Pharmacy, Philadelphia, Pennsylvania.
authors.forename: Emily M
authors.initials: EM
authors.lastname: Scopelliti
authors.affiliation: Department of Pharmacy Practice, Thomas Jefferson University, Jefferson College of Pharmacy, Philadelphia, Pennsylvania.
authors.forename: Julie
authors.initials: J
authors.lastname: Savelloni
mesh_terms: D000924:Anticholesteremic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001562:Benzimidazoles / Q000008:administration & dosage / Q000627:therapeutic use; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000188:drug therapy*; D009841:Oligonucleotides / Q000008:administration & dosage / Q000627:therapeutic use; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases / Q000037:antagonists & inhibitors; D012697:Serine Endopeptidases
chemical_list: D000924:Anticholesteremic Agents; C473731:BMS201038; D001562:Benzimidazoles; D009841:Oligonucleotides; C524142:mipomersen; C472125:PCSK9 protein, human; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases; D012697:Serine Endopeptidases
keywords: alirocumab; evolocumab; familial hypercholesterolemia; heterozygous familial hypercholesterolemia; homozygous familial hypercholesterolemia; lomitapide; mipomersen