Perspectives of the non-statin hypolipidemic agents

Pharmacol Ther. 2010 Jul;127(1):19-40. doi: 10.1016/j.pharmthera.2010.03.007. Epub 2010 Apr 24.


This review focuses on the non-statin strategies for the treatment of hyperlipidemias in humans. Even if statins remain the major hypolipidemic drugs at present, an increasing number of patients that are treated with statins raises as well the numbers of patients suffering from side effects or not responding well to the therapy. Thus, development of novel approaches to battle the world epidemics of hyperlipidemia remains relevant. The non-statin strategies include the decrease of cholesterol absorption from the diet, lowering the atherogenic lipoprotein release and increasing HDL levels, or increasing elimination of cholesterol by bile acid binding. Representative non-statin drugs that are on the market or are in development phases are described herein in comparison to statins. In addition to 3beta-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR), as the major regulatory enzyme of cholesterol synthesis that is the target of statins, some other enzymes of this multi-step pathway represent perspective targets for the development of novel hypolipidemics. None of these inhibitors are currently approved for use in humans. We describe the characteristics of the later enzymes of cholesterol synthesis, starting from the squalene synthase step. Inhibitors of these enzymes are critically evaluated, particularly concerning safety in humans (teratogenic potential, toxicity, and other side effects) and their hypolipidemic effects compared to the statins. Since only a limited number of publications discuss the non-statin approaches for the treatment of hyperlipidemias, this review represents a valuable up-to date summary, with a take-home message, that novel approaches deserve more attention in the future, irrespective of the success of statins.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Anticholesteremic Agents / therapeutic use*
  • Atherosclerosis / enzymology
  • Atherosclerosis / etiology
  • Cholesterol / biosynthesis
  • Cholesterol / metabolism
  • Female
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / adverse effects
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacology
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use*
  • Hypercholesterolemia / drug therapy
  • Hypercholesterolemia / enzymology*
  • Hypolipidemic Agents / therapeutic use*
  • Intestinal Absorption / drug effects
  • Male
  • Risk Factors


  • Anticholesteremic Agents
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Hypolipidemic Agents
  • Cholesterol