Efficacy and safety of a new cholesterol synthesis inhibitor, atorvastatin, in comparison with simvastatin and pravastatin, in subjects with hypercholesterolemia.
BACKGROUND
High levels of total and LDL-cholesterol are associated with an increased risk of atherosclerotic vascular disease. Lowering of serum cholesterol levels by pharmacologic intervention with inhibitors of cholesterol synthesis, the so-called statins, reduces the incidence of cardiovascular events in subjects with and without atherosclerotic manifestations. In a 16-week, multicenter, randomized, open-label cross-over study we compared the efficacy and safety of the new compound atorvastatin for reducing LDL-cholesterol with simvastatin or pravastatin.


METHODS
Following a 4-week placebo-controlled baseline period patients with LDL-cholesterol between 4.1 and 6.2 mmol/l and serum triglycerides below 3.4 mmol/l were randomly assigned to treatment either with 5 or 20 mg atorvastatin, or with 10 mg simvastatin or 20 mg pravastatin once daily for 4 weeks. After a placebo-washout period of 4-6 weeks, patients switched to the alternate treatment. At the end of weeks 3 and 4 of each study phase the serum concentrations of lipid parameters and apolipoproteins as well as safety parameters were determined.


RESULTS
A total of 78 subjects entered the study. Treatment with 5 mg atorvastatin reduced total and LDL-cholesterol by 21 and 27%, respectively, which was similar to 10 mg simvastatin (total cholesterol -20%, LDL-cholesterol -28%) and 20 mg pravastatin (-18 and -24%, respectively). The effects of this low dose of atorvastatin on triglyceride levels (-16%) was not different from that of simvastatin and pravastatin (-8 and -11%, respectively). Treatment with 20 mg atorvastatin caused significantly larger reductions in total cholesterol (-33%) and LDL-cholesterol (-44%), serum triglycerides (-23%), and apo B (-40%) compared to simvastatin and pravastatin. Atorvastatin was well-tolerated, and no serious or medically important adverse events were observed.


CONCLUSIONS
We conclude that atorvastatin is a safe and very efficacious cholesterol-lowering agent, which also possesses significant triglyceride-lowering properties.
Wolffenbuttel
B H
BH
Department of Endocrinology and Metabolism, University Hospital Maastricht, Netherlands. bwo@sint.azm.nl
Mahla
G
G
Muller
D
D
Pentrup
A
A
Black
D M
DM
D000293:Adolescent; D000328:Adult; D000368:Aged; D000924:Anticholesteremic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001055:Apolipoproteins B / Q000097:blood; D000069059:Atorvastatin; D002784:Cholesterol / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood / Q000187:drug effects; D018592:Cross-Over Studies; D005260:Female; D006538:Heptanoic Acids / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D006937:Hypercholesterolemia / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D017035:Pravastatin / Q000627:therapeutic use*; D011758:Pyrroles / Q000009:adverse effects / Q000627:therapeutic use*; D019821:Simvastatin / Q000627:therapeutic use*; D016896:Treatment Outcome; D014280:Triglycerides / Q000097:blood
D000924:Anticholesteremic Agents; D001055:Apolipoproteins B; D008078:Cholesterol, LDL; D006538:Heptanoic Acids; D011758:Pyrroles; D014280:Triglycerides; D002784:Cholesterol; D000069059:Atorvastatin; D019821:Simvastatin; D017035:Pravastatin