title: Expanded Clinical Evaluation of Lovastatin (EXCEL) study results. I. Efficacy in modifying plasma lipoproteins and adverse event profile in 8245 patients with moderate hypercholesterolemia.
abstract: In the Expanded Clinical Evaluation of Lovastatin (EXCEL) Study, a multicenter, double-blind, diet- and placebo-controlled trial, we evaluated the efficacy and safety of lovastatin in 8245 patients with moderate hypercholesterolemia. Patients were randomly assigned to receive placebo or lovastatin at a dosage of 20 mg once daily, 40 mg once daily, 20 mg twice daily, or 40 mg twice daily for 48 weeks. Lovastatin produced sustained, dose-related (P less than .001) changes as follows (for dosages of 20 to 80 mg/d): decreased low-density lipoprotein-cholesterol level (24% to 40%), increased high-density lipoprotein-cholesterol level (6.6% to 9.5%), decreased total cholesterol level (17% to 29%), and decreased triglyceride level (10% to 19%). The National Cholesterol Education Program's low-density lipoprotein-cholesterol level goal of less than 4.14 mmol/L (160 mg/dL) was achieved by 80% to 96% of patients, while the less than 3.36 mmol/L (130 mg/dL) goal was achieved by 38% to 83% of patients. The difference between lovastatin and placebo in the incidence of clinical adverse experiences requiring discontinuation was small, ranging from 1.2% at 20 mg twice daily to 1.9% at 80 mg/d. Successive transaminase level elevations greater than three times the upper limit of normal were observed in 0.1% of patients receiving placebo and 20 mg/d of lovastatin, increasing to 0.9% in those receiving 40 mg/d and 1.5% in those receiving 80 mg/d of lovastatin (P less than .001 for trend). Myopathy, defined as muscle symptoms with a creatine kinase elevation greater than 10 times the upper limit of normal, was found in only one patient (0.1%) receiving 40 mg once daily and four patients (0.2%) receiving 80 mg/d of lovastatin. Thus, lovastatin, when added after an adequate trial of a prudent diet, is a highly effective and generally well-tolerated treatment for patients with moderate hypercholesterolemia.
authors.affiliation: Lipid Research Clinic, Oklahoma Medical Research Foundation, Oklahoma City 73104.
authors.forename: R H
authors.initials: RH
authors.lastname: Bradford
authors.forename: C L
authors.initials: CL
authors.lastname: Shear
authors.forename: A N
authors.initials: AN
authors.lastname: Chremos
authors.forename: C
authors.initials: C
authors.lastname: Dujovne
authors.forename: M
authors.initials: M
authors.lastname: Downton
authors.forename: F A
authors.initials: FA
authors.lastname: Franklin
authors.forename: A L
authors.initials: AL
authors.lastname: Gould
authors.forename: M
authors.initials: M
authors.lastname: Hesney
authors.forename: J
authors.initials: J
authors.lastname: Higgins
authors.forename: D P
authors.initials: DP
authors.lastname: Hurley
mesh_terms: D000328:Adult; D000368:Aged; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D003402:Creatine Kinase / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D006937:Hypercholesterolemia / Q000097:blood / Q000188:drug therapy*; D008074:Lipoproteins / Q000097:blood*; D008111:Liver Function Tests; D008148:Lovastatin / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009135:Muscular Diseases / Q000139:chemically induced; D010349:Patient Compliance; D014280:Triglycerides / Q000097:blood
chemical_list: D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D008074:Lipoproteins; D014280:Triglycerides; D008148:Lovastatin; D003402:Creatine Kinase