Treatment of familial hypercholesterolaemia: a controlled trial of the effects of pravastatin or cholestyramine therapy on lipoprotein and apolipoprotein levels.
The efficacy and safety of a new, selective inhibitor of cholesterol synthesis, pravastatin, and the bile acid-binding resin, cholestyramine, were compared in a randomized, double-blind study of 120 patients with familial hypercholesterolaemia. After a run-in period of 8-10 weeks with assessment of dietary habits, the patients were treated with pravastatin + placebo, placebo + cholestyramine, or placebo alone. Active pravastatin therapy was initiated with 10 mg b.i.d. for 6 weeks, and was increased to 20 mg b.i.d. for the following 6 weeks. Cholestyramine was given at 24 g d-1, or the highest tolerable dose. After 6 weeks of therapy, serum total and LDL cholesterol levels were reduced by 17% and 21%, respectively, on pravastatin treatment, whereas the corresponding reductions with cholestyramine treatment were 24% and 30%, respectively. With an increased dose of pravastatin, serum and LDL cholesterol concentrations were reduced by 23% and 28%, respectively, after 12 weeks; the effect of cholestyramine was unchanged. HDL cholesterol levels increased in response to pravastatin, by 7% and 9% after 6 and 12 weeks, respectively. Concomitant changes in the concentrations of apolipoproteins B and AI were observed. Three patients discontinued the study because of side-effects: two subjects were treated with pravastatin and one was given placebo. The prevalence of side-effects (including laboratory abnormalities) was 35% for pravastatin, 30% for placebo, and 53% (significantly higher) for cholestyramine. We conclude that pravastatin, in a 40 mg daily dose, is as effective as cholestyramine in lowering LDL cholesterol in familial hypercholesterolaemia. Since the frequency of side-effects is higher with cholestyramine, pravastatin offers a promising alternative for the therapy of this genetic disease.
Wiklund
O
O
Department of Medicine I, Sahlgren's Hospital, Göteborg, Sweden.
Angelin
B
B
Fager
G
G
Eriksson
M
M
Olofsson
S O
SO
Berglund
L
L
Lindén
T
T
Sjöberg
A
A
Bondjers
G
G
D000328:Adult; D000368:Aged; D000410:Alanine Transaminase / Q000097:blood; D000924:Anticholesteremic Agents / Q000627:therapeutic use*; D001053:Apolipoproteins / Q000097:blood*; D001219:Aspartate Aminotransferases / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood*; D002792:Cholestyramine Resin / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D006538:Heptanoic Acids / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000097:blood / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009281:Naphthalenes / Q000009:adverse effects / Q000627:therapeutic use*; D017035:Pravastatin; D016032:Randomized Controlled Trials as Topic; D014280:Triglycerides / Q000097:blood
D000924:Anticholesteremic Agents; D001053:Apolipoproteins; D008078:Cholesterol, LDL; D006538:Heptanoic Acids; D009281:Naphthalenes; D014280:Triglycerides; D002792:Cholestyramine Resin; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D017035:Pravastatin