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


METHODS
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 Unpublished data were obtained from the Food and Drug Administration in accordance with the Freedom of Information Act.


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


METHODS
Pertinent studies were selected and the data were synthesized into a review format.


RESULTS
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.
Philadelphia College of Pharmacy and Science, PA, USA.
I
I
Hsu
S A
SA
Spinler
N E
NE
Johnson
D000924:Anticholesteremic Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D002386:Cataract / Q000139:chemically induced; D002986:Clinical Trials as Topic; D017850:Economics, Pharmaceutical; D004791:Enzyme Inhibitors / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D005229:Fatty Acids, Monounsaturated / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D000077340:Fluvastatin; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D006937:Hypercholesterolemia / Q000188:drug therapy*; D007211:Indoles / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D008148:Lovastatin / Q000009:adverse effects / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D017035:Pravastatin / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D019821:Simvastatin
D000924:Anticholesteremic Agents; D004791:Enzyme Inhibitors; D005229:Fatty Acids, Monounsaturated; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007211:Indoles; D000077340:Fluvastatin; D008148:Lovastatin; D019821:Simvastatin; D017035:Pravastatin