Lovastatin (mevinolin) in the treatment of heterozygous familial hypercholesterolemia. A multicenter study.
OBJECTIVE
To evaluate the efficacy and tolerability of lovastatin under controlled conditions in heterozygous familial hypercholesterolemia.


METHODS
Randomized, double-blind, placebo-controlled, multicenter trial.


METHODS
Five lipid clinics with a central laboratory and coordinating center.


METHODS
101 adult patients with heterozygous familial hypercholesterolemia.


METHODS
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.


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 less than 0.01). High-density lipoprotein cholesterol and apolipoproteins AI and AII rose slightly. Apolipoprotein B fell substantially at the higher dosage levels (-23% at 40 mg twice daily, p less than 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 Adverse effects attributable to lovastatin were minimal, and no patient was withdrawn from the study.


CONCLUSIONS
Lovastatin was well tolerated and effective in the treatment of familial hypercholesterolemia.
Havel
R J
RJ
Cardiovascular Research Institute, School of Medicine, University of California, San Francisco.
Hunninghake
D B
DB
Illingworth
D R
DR
Lees
R S
RS
Stein
E A
EA
Tobert
J A
JA
Bacon
S R
SR
Bolognese
J A
JA
Frost
P H
PH
Lamkin
G E
GE
D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D001055:Apolipoproteins B / Q000097:blood; D002386:Cataract / Q000139:chemically induced; D002784:Cholesterol / Q000097:blood; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004341:Drug Evaluation; D005260:Female; D006579:Heterozygote; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000188:drug therapy* / Q000235:genetics; D008148:Lovastatin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D011897:Random Allocation
D001055:Apolipoproteins B; D002784:Cholesterol; D008148:Lovastatin; D000410:Alanine Transaminase