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I. Efficacy in Modifying Plasma Lipoproteins and Adverse Event Profile in 8245 Patients With Moderate Hypercholesterolemia

Reagan H. Bradford, MD, PhD; Charles L. Shear, DPH; Athanassios N. Chremos, MD; Carlos Dujovne, MD; Maria Downton, MS; Frank A. Franklin, MD, PhD; A. Lawrence Gould, PhD; Michael Hesney, MS; Jim Higgins, PhD; Dennis P. Hurley, DSc; Alexandra Langendorfer, MS; David T. Nash, MD; James L. Pool, MD; Harold Schnaper, MD

Arch Intern Med. 1991;151(1):43-49.

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<.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<.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.

(Arch Intern Med. 1991;151:43-49)

Author Affiliations
From the Lipid Research Clinic, Oklahoma Medical Research Foundation, Oklahoma City (Dr Bradford); Merck Sharp & Dohme Research Laboratories, West Point, Pa (Drs Shear, Chremos, and Gould, Mr Hesney, and Ms Langen-dorfer); Lipid and Arteriosclerosis Prevention Clinic, University of Kansas, Kansas City (Dr Dujovne); Clinical Research International Inc, Research Triangle Park, NC (Ms Downton and Drs Higgins and Hurley); Department of Pediatrics, Louisiana State University Medical Center, New Orleans (Dr Franklin); Department of Medicine, State University of New York Health Science Center at Syracuse (Dr Nash); Department of Medicine, Baylor College of Medicine, Houston, Tex (Dr Pool); and Center for Aging, University of Alabama at Birmingham (Dr Schnaper).

Footnotes
Accepted for publication October 31, 1990.

Reprint requests to the Lipid Research Clinic, Oklahoma Medical Research Foundation, 825 Northeast 13th St, Oklahoma City, OK 73104 (Dr Bradford).

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