Pharmacotherapy for dyslipidaemia--current therapies and future agents

Expert Opin Pharmacother. 2003 Nov;4(11):1901-38. doi: 10.1517/14656566.4.11.1901.

Abstract

Current lipid-altering agents that lower low density lipoprotein cholesterol (LDL-C) primarily through increased hepatic LDL receptor activity include statins, bile acid sequestrants/resins and cholesterol absorption inhibitors such as ezetimibe, plant stanols/sterols, polyphenols, as well as nutraceuticals such as oat bran, psyllium and soy proteins; those currently in development include newer statins, phytostanol analogues, squalene synthase inhibitors, bile acid transport inhibitors and SREBP cleavage-activating protein (SCAP) activating ligands. Other current agents that affect lipid metabolism include nicotinic acid (niacin), acipimox, high-dose fish oils, antioxidants and policosanol, whilst those in development include microsomal triglyceride transfer protein (MTP) inhibitors, acylcoenzyme A: cholesterol acyltransferase (ACAT) inhibitors, gemcabene, lifibrol, pantothenic acid analogues, nicotinic acid-receptor agonists, anti-inflammatory agents (such as Lp-PLA(2) antagonists and AGI1067) and functional oils. Current agents that affect nuclear receptors include PPAR-alpha and -gamma agonists, while in development are newer PPAR-alpha, -gamma and -delta agonists, as well as dual PPAR-alpha/gamma and 'pan' PPAR-alpha/gamma/delta agonists. Liver X receptor (LXR), farnesoid X receptor (FXR) and sterol-regulatory element binding protein (SREBP) are also nuclear receptor targets of investigational agents. Agents in development also may affect high density lipoprotein cholesterol (HDL-C) blood levels or flux and include cholesteryl ester transfer protein (CETP) inhibitors (such as torcetrapib), CETP vaccines, various HDL 'therapies' and upregulators of ATP-binding cassette transporter (ABC) A1, lecithin cholesterol acyltransferase (LCAT) and scavenger receptor class B Type 1 (SRB1), as well as synthetic apolipoprotein (Apo)E-related peptides. Fixed-dose combination lipid-altering drugs are currently available such as extended-release niacin/lovastatin, whilst atorvastatin/amlodipine, ezetimibe/simvastatin, atorvastatin/CETP inhibitor, statin/PPAR agonist, extended-release niacin/simvastatin and pravastatin/aspirin are under development. Finally, current and future lipid-altering drugs may include anti-obesity agents which could favourably affect lipid levels.

Publication types

  • Review

MeSH terms

  • Animals
  • Anti-Obesity Agents / therapeutic use
  • Apolipoproteins E / metabolism
  • Cholesterol, Dietary / pharmacokinetics
  • Cholesterol, HDL / blood
  • Drug Combinations
  • Enterohepatic Circulation / physiology
  • Humans
  • Hyperlipidemias / drug therapy*
  • Hypolipidemic Agents / pharmacology
  • Hypolipidemic Agents / therapeutic use*
  • Lipid Metabolism
  • Receptors, Cytoplasmic and Nuclear / drug effects
  • Receptors, Cytoplasmic and Nuclear / metabolism
  • Receptors, LDL / drug effects
  • Receptors, LDL / metabolism

Substances

  • Anti-Obesity Agents
  • Apolipoproteins E
  • Cholesterol, Dietary
  • Cholesterol, HDL
  • Drug Combinations
  • Hypolipidemic Agents
  • Receptors, Cytoplasmic and Nuclear
  • Receptors, LDL