A comparison of simvastatin and atorvastatin up to maximal recommended doses in a large multicenter randomized clinical trial

D. R. Illingworth, J. R. Crouse, D. B. Hunninghake, M. H. Davidson, I. D. Escobar, A. F.H. Stalenhoef, G. Paragh, S. P. T., M. Liu, M. R. Melino, L. O'Grady, M. Mercuri, Y. B. Mitchel

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Abstract

Objective: At higher doses, simvastatin has been shown to produce significantly greater increases in high-density lipoprotein (HDL) cholesterol and apolipoprotein (apo) A-I than atorvastatin. To extend and confirm these findings, a 36-week, randomized, double-blind, dose-titration study was performed in 826 hypercholesterolemic patients to compare the effects of simvastatin and atorvastatin on HDL cholesterol, apo A-I, and clinical and laboratory safety. Primary hypothesis: Simvastatin, across a range of doses, will be more effective than atorvastatin at raising HDL cholesterol and apo A-I levels. Methods: A total of 826 hypercholesterolemic patients were enrolled in this double-blind, randomized, parallel, 36-week, dose-escalation study. Patients randomized to simvastatin received 40 mg/day for the first 6 weeks, 80 mg/day for the next 6 weeks, and remained on 80 mg/day for the final 24 weeks. Patients randomized to atorvastatin received 20 mg/day for the first 6 weeks, 40 mg/day for the next 6 weeks, and 80 mg/day for the remaining 24 weeks. Results: During the first 12 weeks of the study, simvastatin increased HDL cholesterol and apo A-I more than the comparative doses of atorvastatin, while producing slightly lower reductions in low-density lipoprotein (LDL) cholesterol and triglycerides. At the maximal dose comparison, simvastatin 80 mg and atorvastatin 80 mg, the HDL cholesterol and apo A-I differences favoring simvastatin were larger than at the lower doses. In addition, at the maximal dose comparison, the incidence of drug-related clinical adverse experiences was approximately two-fold higher with atorvastatin 80 mg than with simvastatin 80 mg (23 versus 12%, p < 0.001), due predominantly to a greater incidence of gastrointestinal symptoms with atorvastatin (10 versus 3%, p < 0.001). The incidence of clinically significant alanine aminotransferase elevations was also higher with atorvastatin 80 mg than with simvastatin 80 mg (3.8 versus 0.5%, p < 0.010), especially in women (6.0 versus 0.6%). Conclusions: At the doses compared in this study, simvastatin led to greater increases in HDL cholesterol and apo A-I levels than atorvastatin. At the maximum dose comparison, there were fewer drug-related gastrointestinal symptoms and clinically significant aminotransferase elevations with simvastatin.

Original languageEnglish
Pages (from-to)43-50
Number of pages8
JournalCurrent Medical Research and Opinion
Volume17
Issue number1
DOIs
Publication statusPublished - Jul 11 2001

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Keywords

  • Apolipoproteins
  • HDL-Cholesterol
  • Hypercholesterolemia
  • Lipids

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Illingworth, D. R., Crouse, J. R., Hunninghake, D. B., Davidson, M. H., Escobar, I. D., Stalenhoef, A. F. H., Paragh, G., T., S. P., Liu, M., Melino, M. R., O'Grady, L., Mercuri, M., & Mitchel, Y. B. (2001). A comparison of simvastatin and atorvastatin up to maximal recommended doses in a large multicenter randomized clinical trial. Current Medical Research and Opinion, 17(1), 43-50. https://doi.org/10.1185/03007990152005351