Comparative evaluation of the safety and efficacy of HMG-CoA reductase inhibitor monotherapy in the treatment of primary hypercholesterolemia

Ann Pharmacother. Jul-Aug 1995;29(7-8):743-59. doi: 10.1177/106002809502907-818.


Objective: To evaluate the comparative efficacy and safety of the 4 currently available hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors, fluvastatin, lovastatin, pravastatin, and simvastatin, in the treatment of primary hypercholesterolemia.

Data sources: English-language clinical studies, abstracts, and review articles identified from MEDLINE searches and bibliographies of identified articles. Unpublished data were obtained from the Food and Drug Administration in accordance with the Freedom of Information Act.

Study selection: Placebo-controlled and comparative studies of HMG-CoA reductase inhibitor monotherapy in the treatment of primary hypercholesterolemia.

Data extraction: Pertinent studies were selected and the data were synthesized into a review format.

Data synthesis: The chemistry, pharmacology, and pharmacokinetics of the 4 HMG-CoA reductase inhibitors are reviewed. Clinical trials evaluating the hypocholesterolemic efficacy of the HMG-CoA reductase inhibitors are examined, and results on the comparative efficacy and safety of these agents are summarized. On a milligram-per-milligram basis, simvastatin is twice as potent as lovastatin and pravastatin. The hypocholesterolemic effects of fluvastatin appear to be approximately 30% less than that of lovastatin. In posttransplant patients receiving cyclosporine, safety has been documented for low doses of lovastatin and simvastatin, but when a higher dosage of an HMG-CoA reductase inhibitor is warranted, pravastatin should be considered the drug of choice because of a lower incidence of myopathy. Relevant data on the incidence of adverse effects are presented. Pertinent outcomes data from clinical trials evaluating the effect of HMG-CoA reductase inhibitors on atherosclerosis regression and coronary mortality, as well as published economic analyses of cholesterol-lowering agents, are summarized. Recommendations on the selection of an HMG-CoA reductase inhibitor in various clinical situations are provided.

Conclusions: The literature supports the comparable safety and tolerability of all 4 currently available HMG-CoA reductase inhibitors. Therefore, the choice of an HMG-CoA reductase inhibitor should depend on the extent of cholesterol lowering needed to meet the recommended treatment goal established by the National Cholesterol Education Program. Direct comparative studies are needed to confirm the relative, long-term cost-effectiveness of the various HMG-CoA reductase inhibitors in the treatment of primary hypercholesterolemia.

Publication types

  • Comparative Study
  • Review

MeSH terms

  • Anticholesteremic Agents / adverse effects
  • Anticholesteremic Agents / pharmacology
  • Anticholesteremic Agents / therapeutic use*
  • Cataract / chemically induced
  • Clinical Trials as Topic
  • Economics, Pharmaceutical
  • Enzyme Inhibitors / adverse effects
  • Enzyme Inhibitors / pharmacology
  • Enzyme Inhibitors / therapeutic use*
  • Fatty Acids, Monounsaturated / adverse effects
  • Fatty Acids, Monounsaturated / pharmacology
  • Fatty Acids, Monounsaturated / therapeutic use
  • Fluvastatin
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Hypercholesterolemia / drug therapy*
  • Indoles / adverse effects
  • Indoles / pharmacology
  • Indoles / therapeutic use
  • Lovastatin / adverse effects
  • Lovastatin / analogs & derivatives
  • Lovastatin / pharmacology
  • Lovastatin / therapeutic use
  • Pravastatin / adverse effects
  • Pravastatin / pharmacology
  • Pravastatin / therapeutic use
  • Simvastatin


  • Anticholesteremic Agents
  • Enzyme Inhibitors
  • Fatty Acids, Monounsaturated
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Indoles
  • Fluvastatin
  • Lovastatin
  • Simvastatin
  • Pravastatin