title: New therapies to reduce low-density lipoprotein cholesterol.
abstract: OBJECTIVE
  Lipid-lowering is an intervention that reduces atherosclerosis and its complications. Statins currently form the standard of care but are not able to reduce low-density lipoprotein cholesterol (LDL-C) adequately in all patients - particularly those with familial hypercholesterolaemia and those with statin intolerance.
  
  
  RESULTS
  Combination therapy with statins is well established and ezetimibe is often used as an additional LDL-C-lowering agent reducing LDL-C by 20%. However, its clinical efficacy still remains controversial. Newer, more potent methods of LDL-C reduction are in development. Both lomitapide, a microsomal transfer protein inhibitor (MTPI), and mipomersen, an antisense oligonucleotide (ASO), have been shown to improve LDL-C levels by 25-50% in patients with homozygous familial hypercholesterolaemia. In patients with heterozygous familial hypercholesterolaemia or statin intolerance antibody-based inhibitors of preprotein convertase subtilisin/kexin 9 (PCSK9) produce reductions in LDL-C of 30-65%. Cholesterol ester transfer protein inhibitors (CETPIs) reduce LDL-C by 30-40% as well as raising levels of high-density lipoprotein cholesterol (HDL-C) and may also have a role as additional LDL-C-reducing drugs.
  
  
  CONCLUSIONS
  Surrogate outcome trials will be required with lomitapide or mipomersen to confirm their effects in homozygous familial hypercholesterolaemia and clinical endpoint trials will be needed for PCSK9 and CETPIs if these are to be used widely.
authors.affiliation: Guy's & St Thomas' Hospitals, St Thomas' Hospital Campus, London, UK. Anthony.Wierzbicki@kcl.ac.uk
authors.forename: Anthony S
authors.initials: AS
authors.lastname: Wierzbicki
authors.forename: Adie
authors.initials: A
authors.lastname: Viljoen
authors.forename: Timothy C
authors.initials: TC
authors.lastname: Hardman
authors.forename: Dimitri P
authors.initials: DP
authors.lastname: Mikhailidis
mesh_terms: D000924:Anticholesteremic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002352:Carrier Proteins / Q000037:antagonists & inhibitors; D053480:Cholesterol Ester Transfer Proteins / Q000037:antagonists & inhibitors; D008078:Cholesterol, LDL / Q000097:blood*; D002986:Clinical Trials as Topic; D006801:Humans; D006937:Hypercholesterolemia / Q000188:drug therapy*; D016376:Oligonucleotides, Antisense / Q000627:therapeutic use; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases / Q000037:antagonists & inhibitors; D012697:Serine Endopeptidases
chemical_list: D000924:Anticholesteremic Agents; D002352:Carrier Proteins; D053480:Cholesterol Ester Transfer Proteins; D008078:Cholesterol, LDL; D016376:Oligonucleotides, Antisense; C106092:microsomal triglyceride transfer protein; C472125:PCSK9 protein, human; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases; D012697:Serine Endopeptidases