title: Using changes in attributable risk to predict long-term efficacy of simvastatin treatment.
abstract: It is a common perception that coronary heart disease (CHD) deaths will decline by 2% for every 1% decrease in serum total cholesterol (TC). We investigated the changes in serum TC concentrations obtained with simvastatin, an inhibitor of hydroxymethylglutaryl-CoA reductase, in 70 hypercholesterolemic subjects. Although simvastatin reduced serum TC concentrations by 30% after 6 months, calculations from age- and risk-related TC quintiles show that the absolute difference in attributable CHD deaths would be just > 1%. These results are reminiscent of the experience from several large prospective primary drug trials that demonstrated impressive relative benefit ratios but much smaller absolute differences (< 2%) in CHD endpoints between the treated and untreated groups. This epidemiologically based approach of assessing efficacy and potential long-term benefit of a lipid-lowering drug may be more appropriate and potentially less misleading than just the percentage change of TC (or other lipoproteins) so frequently reported in short-term drug trials.
authors.affiliation: Department of Chemical Pathology, Faculty of Medicine, University of Pretoria, South Africa.
authors.forename: W J
authors.initials: WJ
authors.lastname: Vermaak
authors.forename: J B
authors.initials: JB
authors.lastname: Ubbink
authors.forename: J P
authors.initials: JP
authors.lastname: Ungerer
authors.forename: A D
authors.initials: AD
authors.lastname: Marais
authors.forename: J
authors.initials: J
authors.lastname: Firth
authors.forename: J M
authors.initials: JM
authors.lastname: Van Lathem
authors.forename: P J
authors.initials: PJ
authors.lastname: Becker
mesh_terms: D000328:Adult; D000924:Anticholesteremic Agents / Q000627:therapeutic use*; D002784:Cholesterol / Q000097:blood*; D003327:Coronary Disease / Q000097:blood / Q000517:prevention & control; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D006937:Hypercholesterolemia / Q000097:blood / Q000188:drug therapy*; D008148:Lovastatin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D019821:Simvastatin
chemical_list: D000924:Anticholesteremic Agents; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D002784:Cholesterol; D008148:Lovastatin; D019821:Simvastatin