New drugs for the treatment of hypercholesterolaemia

Expert Opin Investig Drugs. 2003 Nov;12(11):1777-89. doi: 10.1517/13543784.12.11.1777.


Endogenous and exogenous pathways determine plasma levels of cholesterol and lipoproteins. Plasma cholesterol levels and coronary heart disease risk can be reduced pharmacologically by decreasing cholesterol synthesis, increasing its elimination and/or reducing its absorption from the intestine. The more profound knowledge about cholesterol homeostasis has allowed the development of several lipid-lowering drugs with different mechanisms of action, with the purpose of reducing both morbidity and mortality associated with coronary heart disease. Two new and more potent 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins), also called superstatins (rosuvastatin and pitavastatin), are being studied for their ability to improve lipid profiles. Rosuvastatin is a potent, hepato-selective and relatively hydrophilic statin with a low propensity for muscle toxicity and drug interactions. Pitavastatin is another statin with a high oral bioavailability and minimal propensity for cytochrome p450-mediated drug interactions. Rosuvastatin seems to be more potent than other available statins while pitavastatin presents with a similar potency to that of atorvastatin. Another promising approach for lowering total and low-density lipoprotein cholesterol levels is inhibition of cholesterol absorption. A wide variety of new agents with the capacity for inhibiting the intestinal cholesterol absorption is currently being investigated. Ezetimibe is a selective cholesterol absorption inhibitor whose clinical efficacy has been recently demonstrated both in monotherapy and in combination with other lipid-lowering drugs. Colesevelam, a new bile acid sequestrant, has shown a clinical efficacy similar to that of other resins, with minimal gastrointestinal side effects, improving tolerability and patient compliance. Other lipid-lowering drugs with the ability to act at the enterocyte level, such as avasimibe and implitapide, are currently being investigated in humans.

Publication types

  • Review

MeSH terms

  • Absorption
  • Anticholesteremic Agents / pharmacology
  • Anticholesteremic Agents / therapeutic use*
  • Cholesterol / biosynthesis
  • Cholesterol / metabolism
  • Clinical Trials as Topic
  • Coronary Disease / etiology
  • Coronary Disease / prevention & control
  • Drug Design
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / adverse effects
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacokinetics
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use
  • Hypercholesterolemia / complications
  • Hypercholesterolemia / drug therapy*
  • Intestinal Mucosa / metabolism


  • Anticholesteremic Agents
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Cholesterol