New therapeutic principles in dyslipidaemia: focus on LDL and Lp(a) lowering drugs

Eur Heart J. 2013 Jun;34(24):1783-9. doi: 10.1093/eurheartj/eht088. Epub 2013 Mar 18.

Abstract

Dyslipidaemias play a key role in determining cardiovascular risk; the discovery of statins has contributed a very effective approach. However, many patients do not achieve, at the maximal tolerated dose, the recommended goals for low-density lipoprotein-cholesterol (LDL-C), non-high-density lipoprotein-cholesterol, and apolipoprotein B (apoB). Available agents combined with statins can provide additional LDL-C reduction, and agents in development will increase therapeutic options impacting also other atherogenic lipoprotein classes. In fact, genetic insights into mechanisms underlying regulation of LDL-C levels has expanded potential targets of drug therapy and led to the development of novel agents. Among them are modulators of apoB containing lipoproteins production and proprotein convertase subtilisin/kexin type-9 inhibitors. Alternative targets such as lipoprotein(a) also require attention; however, until we have a better understanding of these issues, further LDL-C lowering in high and very high-risk patients will represent the most sound clinical approach.

Keywords: Apolipoprotein B; Dyslipidaemia; PCSK9; Pharmacology.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Azetidines / therapeutic use
  • Benzimidazoles / therapeutic use
  • Benzodiazepines / therapeutic use
  • Carrier Proteins / antagonists & inhibitors
  • Cholesterol, LDL / antagonists & inhibitors
  • Cholesterol, LDL / drug effects*
  • Dicarboxylic Acids / therapeutic use
  • Dyslipidemias / drug therapy*
  • Ezetimibe
  • Fatty Acids / therapeutic use
  • Humans
  • Hypolipidemic Agents / therapeutic use*
  • Lipoprotein(a) / antagonists & inhibitors
  • Lipoprotein(a) / drug effects*
  • Oligonucleotides / therapeutic use
  • Oxazolidinones / therapeutic use
  • Proprotein Convertase 9
  • Proprotein Convertases / antagonists & inhibitors
  • Serine Endopeptidases

Substances

  • Azetidines
  • BMS201038
  • Benzimidazoles
  • Carrier Proteins
  • Cholesterol, LDL
  • Dicarboxylic Acids
  • Fatty Acids
  • Hypolipidemic Agents
  • Lipoprotein(a)
  • Oligonucleotides
  • Oxazolidinones
  • microsomal triglyceride transfer protein
  • Benzodiazepines
  • 8-hydroxy-2,2,14,14-tetramethylpentadecanedioic acid
  • evacetrapib
  • mipomersen
  • PCSK9 protein, human
  • Proprotein Convertase 9
  • Proprotein Convertases
  • Serine Endopeptidases
  • Ezetimibe
  • anacetrapib