Expanded clinical evaluation of lovastatin (EXCEL) study: design and patient characteristics of a double-blind, placebo-controlled study in patients with moderate hypercholesterolemia.
The randomized, double-blind, placebo-controlled trial described in this report was undertaken to clarify the dose-response relation of lovastatin therapy to lipid-modifying efficacy (lipid/lipoprotein modification) and drug-related adverse events in a population with moderately elevated fasting plasma total cholesterol (240 to 300 mg/dl) and low-density lipoprotein cholesterol (greater than or equal to 160 mg/dl). Men or women (postmenopausal or surgically sterile), aged 18 to 70 years, were entered into the trial with minimal exclusion criteria. After 4 to 6 weeks of an American Heart Association phase I diet or a more stringent diet, 8,245 patients from 362 sites were randomized to 1 of 5 parallel diet and drug treatment groups: placebo (n = 1,663) or lovastatin, 20 mg (n = 1,642) and 40 mg (n = 1,645) with the evening meal, and 20 mg (n = 1,646) or 40 mg twice daily (n = 1,649). The regimen of diet and lovastatin (or placebo) was followed for 48 weeks. The 5 treatment groups were similar at baseline. The total cohort had the following characteristics: 59% were men (mean age 56 years); 92% were white; 59% had completed at least 1 year of education beyond high school; 57% had a history of cardiovascular and associated disease; 40% had a history of hypertension; and 29% had coronary artery disease. Health habits were similar among groups, with 18% of patients reporting cigarette smoking, 14% reporting that they consume greater than 1 alcoholic beverage daily and 67% reporting no strenous exercise. Mean lipid/lipoprotein levels were also similar among groups, with the following average levels: total cholesterol (258 mg/dl), low-density lipoprotein cholesterol (180 mg/dl), high-density lipoprotein cholesterol (45 mg/dl) and triglycerides (median = 155 mg/dl). The large size of this trial, its placebo-controlled, double-blind design and the similarity of treatment groups at baseline should allow clear documentation of the long-term effects of lovastatin treatment and generalization of the results to a substantial portion of patients who may be candidates for lipid-modifying therapy.
Bradford
R H
RH
Lipid Research Clinic, Oklahoma Medical Research Foundation, Oklahoma City 73104.
Shear
C L
CL
Chremos
A N
AN
Dujovne
C
C
Franklin
F A
FA
Hesney
M
M
Higgins
J
J
Langendörfer
A
A
Pool
J L
JL
Schnaper
H
H
D000328:Adult; D000368:Aged; D002784:Cholesterol / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D006937:Hypercholesterolemia / Q000188:drug therapy*; D008148:Lovastatin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D010919:Placebos; D016032:Randomized Controlled Trials as Topic; D014280:Triglycerides / Q000097:blood
D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D010919:Placebos; D014280:Triglycerides; D002784:Cholesterol; D008148:Lovastatin