Pharmacotherapy of hypercholesterolaemia: statins in clinical practice

Expert Opin Pharmacother. 2000 May;1(4):683-95. doi: 10.1517/14656566.1.4.683.

Abstract

The objective of this article is to evaluate the roles of the lipid-lowering class of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) in reducing cardiovascular events and to review their mechanism of action based on in vitro and in vivo studies. The clinical outcome of 15 major clinical trials has been critically reviewed and summarised; all showed a high degree of efficacy and safety. Statins, either in active or prodrug forms, are potent inhibitors of HMG-CoA reductase, have good absorption rate and their bioavailability depends on their lipophobicity and concomitant use with meals. Abdominal discomfort is the most commonly reported adverse effect. Although the incidence is low, myopathy with or without rhabdomyolysis may be considered a serious adverse effect of statins. A combination of a statin with gemfibrozil seems to increase the risk of this adverse event, particularly in patients with renal impairment. Combination therapy with several other agents, frequently administered to cardiovascular patients, has also been reviewed. Statin therapy is considered highly cost effective in secondary prevention, but it is less cost effective in primary prevention. This factor may underline the rationale for developing other safe and effective agents with an improved cost effectiveness profile. The pleiotropic non-lipid lowering effects of statins may include their anti-oxidant and antithrombotic potential as well as restoration of endothelial function. Statins may also be beneficial in the treatment of osteoporosis. Fewer studies have investigated statins' effects on the quality of lipoprotein particles, the activities of cholesteryl ester transfer protein and lecithin:cholesterol acyltransferase as well as their possible synergistic effects with n-3 fatty acids, anti-oxidants and aspirin in reducing cardiovascular events.

Publication types

  • Review

MeSH terms

  • Anticholesteremic Agents / adverse effects
  • Anticholesteremic Agents / chemistry
  • Anticholesteremic Agents / economics
  • Anticholesteremic Agents / pharmacokinetics
  • Anticholesteremic Agents / therapeutic use*
  • Contraindications
  • Drug Therapy, Combination
  • Humans
  • Hypercholesterolemia / drug therapy*
  • Hypercholesterolemia / economics

Substances

  • Anticholesteremic Agents