1. A comparison of simvastatin and atorvastatin up to maximal recommended doses in a large multicenter randomized clinical trial.
- Author
-
Illingworth DR, Crouse JR 3rd, Hunninghake DB, Davidson MH, Escobar ID, Stalenhoef AF, Paragh G, Ma PT, Liu M, Melino MR, O'Grady L, Mercuri M, and Mitchel YB
- Subjects
- Adult, Aged, Anticholesteremic Agents administration & dosage, Anticholesteremic Agents adverse effects, Apolipoprotein A-I blood, Atorvastatin, Cholesterol, HDL blood, Cholesterol, LDL blood, Double-Blind Method, Female, Heptanoic Acids administration & dosage, Heptanoic Acids adverse effects, Humans, Hydroxymethylglutaryl-CoA Reductase Inhibitors administration & dosage, Hydroxymethylglutaryl-CoA Reductase Inhibitors adverse effects, Hypercholesterolemia blood, Male, Middle Aged, Pyrroles administration & dosage, Pyrroles adverse effects, Simvastatin administration & dosage, Simvastatin adverse effects, Treatment Outcome, United States, Anticholesteremic Agents therapeutic use, Heptanoic Acids therapeutic use, Hydroxymethylglutaryl-CoA Reductase Inhibitors therapeutic use, Hypercholesterolemia drug therapy, Lipids blood, Pyrroles therapeutic use, Simvastatin therapeutic use
- 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.
- Published
- 2001