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 cu rrently 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 f rom MEDLINE searches and bibliographies of identified articles, Unpubl ished data were obtained from the Food and Drug Administration in acco rdance with the Freedom of Information Act. STUDY SELECTION: Placebo-c ontrolled and comparative studies of HMG-CoA reductase inhibitor monot herapy in the treatment of primary hypercholesterolemia. DATA EXTRACTI ON: Pertinent studies were selected and the data were synthesized into a review format. DATA SYNTHESIS: The chemistry, pharmacology; and pha rmacokinetics of the 4 HMG-CoA reductase inhibitors are reviewed. Clin ical trials evaluating the hypocholesterolemic efficacy of the HMG-CoA reductase inhibitors are examined, and results on the comparative eff icacy and safety of these agents are summarized. On a milligram-per-mi lligram basis, simvastatin is twice as potent as lovastatin and pravas tatin. The hypocholesterolemic effects of fluvastatin appear to be app roximately 30% less than that of lovastatin. In posttransplant patient s receiving cyclosporine, safety has been documented far low doses of lovastatin and simvastatin, but when a higher dosage of an HMG-CoA red uctase inhibitor is warranted, pravastatin should be considered the dr ug of choice because of a lower incidence of myopathy. Relevant data o n the incidence of adverse effects are presented. Pertinent outcomes d ata from clinical trials evaluating the effect of HMG-CoA reductase in hibitors on atherosclerosis regression and coronary mortality, as well as published economic analyses of cholesterol-lowering agents, are su mmarized, Recommendations on the selection of an HMG-CoA reductase inh ibitor in various clinical situations are provided. CONCLUSIONS: The l iterature supports the comparable safety and tolerability of all 4 cur rently available HMG-CoA reductase inhibitors. Therefore, the choice o f an HMG-CoA reductase inhibitor should depend on the extent of choles terol lowering needed to meet the recommended treatment goal establish ed by the National Cholesterol Education Program. Direct comparative s tudies are needed to confirm the relative, long-term cost-effectivenes s of the various HMG-CoA reductase inhibitors in the treatment of prim ary hypercholesterolemia.