Efficacy and safety of a new cholesterol synthesis inhibitor, atorvastatin, in comparison with simvastatin and pravastatin, in subjects with hypercholesterolemia.

B.H.R. Wolffenbuttel*, G. Mahla, D. Muller, A. Pentrup, D.A. Black

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


Department of Endocrinology and Metabolism, University Hospital Maastricht, Netherlands. bwo@sint.azm.nl

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.

Publication Types:
Clinical Trial
Multicenter Study
Randomized Controlled Trial
Original languageEnglish
Pages (from-to)131-137
Number of pages7
JournalNetherlands Journal of Medicine
Issue number4
Publication statusPublished - 1 Jan 1998


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