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

D. Roger Illingworth, John R. Crouse, Donald B. Hunninghake, Michael H. Davidson, Ivan D. Escobar, Anton F H Stalenhoef, G. Paragh, Patrick T S Ma, Minzhi Liu, Michael R. Melino, Laura O'Grady, Michele Mercuri, Yale B. Mitchel

Research output: Contribution to journalArticle

73 Citations (Scopus)

Abstract

Objective: M. 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 40mg/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 apoA-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, Supplement
Volume17
Issue number1
Publication statusPublished - 2000

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Simvastatin
Randomized Controlled Trials
Apolipoprotein A-I
HDL Cholesterol
Incidence
Atorvastatin Calcium
Gastrointestinal Agents
Transaminases
Alanine Transaminase
LDL Cholesterol
Safety

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., ... Mitchel, Y. B. (2000). A comparison of simvastatin and atorvastatin up to maximal recommended doses in a large multicenter randomized clinical trial. Current Medical Research and Opinion, Supplement, 17(1), 43-50.

A comparison of simvastatin and atorvastatin up to maximal recommended doses in a large multicenter randomized clinical trial. / Illingworth, D. Roger; Crouse, John R.; Hunninghake, Donald B.; Davidson, Michael H.; Escobar, Ivan D.; Stalenhoef, Anton F H; Paragh, G.; Ma, Patrick T S; Liu, Minzhi; Melino, Michael R.; O'Grady, Laura; Mercuri, Michele; Mitchel, Yale B.

In: Current Medical Research and Opinion, Supplement, Vol. 17, No. 1, 2000, p. 43-50.

Research output: Contribution to journalArticle

Illingworth, DR, Crouse, JR, Hunninghake, DB, Davidson, MH, Escobar, ID, Stalenhoef, AFH, Paragh, G, Ma, PTS, Liu, M, Melino, MR, O'Grady, L, Mercuri, M & Mitchel, YB 2000, 'A comparison of simvastatin and atorvastatin up to maximal recommended doses in a large multicenter randomized clinical trial', Current Medical Research and Opinion, Supplement, vol. 17, no. 1, pp. 43-50.
Illingworth, D. Roger ; Crouse, John R. ; Hunninghake, Donald B. ; Davidson, Michael H. ; Escobar, Ivan D. ; Stalenhoef, Anton F H ; Paragh, G. ; Ma, Patrick T S ; Liu, Minzhi ; Melino, Michael R. ; O'Grady, Laura ; Mercuri, Michele ; Mitchel, Yale B. / A comparison of simvastatin and atorvastatin up to maximal recommended doses in a large multicenter randomized clinical trial. In: Current Medical Research and Opinion, Supplement. 2000 ; Vol. 17, No. 1. pp. 43-50.
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T1 - A comparison of simvastatin and atorvastatin up to maximal recommended doses in a large multicenter randomized clinical trial

AU - Illingworth, D. Roger

AU - Crouse, John R.

AU - Hunninghake, Donald B.

AU - Davidson, Michael H.

AU - Escobar, Ivan D.

AU - Stalenhoef, Anton F H

AU - Paragh, G.

AU - Ma, Patrick T S

AU - Liu, Minzhi

AU - Melino, Michael R.

AU - O'Grady, Laura

AU - Mercuri, Michele

AU - Mitchel, Yale B.

PY - 2000

Y1 - 2000

N2 - Objective: M. 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 40mg/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 apoA-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.

AB - Objective: M. 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 40mg/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 apoA-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.

KW - Apolipoproteins

KW - HDL-Cholesterol

KW - Hypercholesterolemia

KW - Lipids

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