Efficacy and Tolerability of Lovastatin in 3390 Women with Moderate Hypercholesterolemia

doi:10.1059/0003-4819-118-11-199306010-00004

Efficacy and Tolerability of Lovastatin in 3390 Women with Moderate Hypercholesterolemia

From Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma; ClinTrials, Inc., Research Triangle Park, North Carolina; Merck Research Laboratories, West Point, PA; State University of New York Health Science Center at Syracuse, New York. Requests for Reprints: Reagan H. Bradford, MD, PhD, Oklahoma Medical Research Foundation, 825 Northeast 13th Street, Oklahoma City, OK 73104. Acknowledgments: The authors thank the investigators (listed in reference 7) who made this study possible. They also thank Patience Vanderbush for editorial assistance. Grant Support: In part by grants to clinical sites from ClinTrials Inc., Research Triangle Park, North Carolina, which was responsible for the execution of this study sponsored by Merck & Co., Inc., Rahway, New Jersey.

Abstract

Objective: To evaluate the efficacy and safety of lovastatin in women with moderate hypercholesterolemia.

Design: The Expanded Clinical Evaluation of Lovastatin (EXCEL) Study, a multicenter, double-blind, diet- and placebo-controlled trial, in which participants were randomly assigned to receive placebo or lovastatin at doses of 20 or 40 mg once daily, or 20 or 40 mg twice daily for 48 weeks.

Setting: Ambulatory patients recruited by 362 participating centers throughout the United States.

Patients: Women (n = 3390) from the total cohort of 8245 volunteers.

Measurements: Plasma total, low-density lipoprotein (LDL), and high-density lipoprotein (HDL) cholesterol, and triglycerides; and laboratory and clinical evidence of adverse events monitored periodically throughout the study.

Results: Among women, lovastatin (20 to 80 mg/d) produced sustained (12- to 48-week), dose-related changes (P < 0.001): decreases in LDL cholesterol (24% to 40%) and triglycerides (9% to 18%), and increases in HDL cholesterol (6.7% to 8.6%). Depending on the dose, from 82% to 95% of lovastatin-treated women achieved the National Cholesterol Education Program goal of LDL cholesterol levels less than 4.14 mmol/L (160 mg/dL), and 40% to 87% achieved the goal of 3.36 mmol/L (130 mg/dL). Successive transaminase elevations greater than three times the upper limit of normal occurred in 0.1% of women and were dose dependent above the 20-mg dose. Myopathy, defined as muscle symptoms with creatine kinase elevations greater than 10 times the upper limit of normal, was rare and associated with the highest recommended daily dose of lovastatin (80 mg). Estrogen-replacement therapy appeared to have no effect on either the efficacy or safety profile of lovastatin.

Conclusion: Lovastatin is highly effective and generally well tolerated as therapy for primary hypercholesterolemia in women.