RICHARD J. HAVEL, M.D.; DONALD B. HUNNINGHAKE, M.D.; D. ROGER ILLINGWORTH, M.D., Ph.D.; ROBERT S. LEES, M.D.; EVAN A. STEIN, M.D., Ph.D.; JONATHAN A. TOBERT, M.B., Ph.D.; SANDRA R. BACON, R.N.; JAMES A. BOLOGNESE, M. Stat; PHILIP H. FROST, M.D.; GLENN E. LAMKIN, M.Ed.; ANN M. LEES, M.D.; ARTHUR S. LEON, M.D.; KAY GARDNER; G. JOHNSON, M.D.; M. J. MELLIES, M.D.; PATRICIA A. RHYMER, M.S.; P. TUN, M.D.
Study Objective: To evaluate the efficacy and tolerability of lovastatin under controlled conditions in heterozygous familial hypercholesterolemia.
Design: Randomized, double-blind, placebo-controlled, multicenter trial.
Setting: Five lipid clinics with a central laboratory and coordinating center.
Patients: 101 adult patients with heterozygous familial hypercholesterolemia.
Interventions: Patients were on a lipid-lowering diet throughout the study. After a 4-week placebo baseline period, patients were randomized to five equal treatment groups. Each group received a different sequence of placebo or lovastatin 5 to 40 mg twice daily or 20 to 40 mg once daily in the evening, during three consecutive 6-week periods.
Measurements and Main Results: The mean reductions in total plasma cholesterol and low-density lipoprotein cholesterol across the dosage ranges were 14% to 34% and 17% to 39%, respectively (p compared with zero and placebo < 0.01). High-density lipoprotein cholesterol and apolipoproteins Al and All rose slightly. Apolipoprotein B fell substantially at the higher dosage levels (-23% at 40 mg twice daily, p < 0.01), indicating a reduction in the concentration of circulating low-density lipoprotein particles. Maximum response was achieved in 4 to 6 weeks. Twice-daily dosing was slightly more efficient than once-daily dosing. Of those patients receiving 40 mg twice a day, 89% had a fall in low-density lipoprotein cholesterol of at least 20%, and 61% had a fall of at least 40%. Adverse effects attributable to lovastatin were minimal, and no patient was withdrawn from the study.
Conclusion: Lovastatin was well tolerated and effective in the treatment of familial hypercholesterolemia.
RICHARD J. HAVEL, DONALD B. HUNNINGHAKE, D. ROGER ILLINGWORTH, ROBERT S. LEES, EVAN A. STEIN, JONATHAN A. TOBERT, et al. Lovastatin (Mevinolin) in the Treatment of Heterozygous Familial Hypercholesterolemia: A Multicenter Study. Ann Intern Med. 1987;107:609–615. doi: 10.7326/0003-4819-107-5-609
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Published: Ann Intern Med. 1987;107(5):609-615.
Cardiology, Coronary Risk Factors, Dyslipidemia.
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