Effect on high-density lipoprotein cholesterol of maximum dose simvastatin and atorvastatin in patients with hypercholesterolemia: results of the Comparative HDL Efficacy and Safety Study (CHESS)

Am Heart J. 2003 Nov;146(5):862-9. doi: 10.1016/S0002-8703(03)00440-X.

Abstract

Background: Previous studies have shown that effects on high-density lipoprotein cholesterol (HDL-C) may differ among statins.

Methods: A multicenter, randomized, double-blind, parallel-dose study was conducted in 917 hypercholesterolemic patients to compare the efficacy of 80 mg/d simvastatin versus 80 mg/d atorvastatin on HDL-C and apolipoprotein (apo) A-I for 24 weeks. Efficacy was assessed as the means of weeks 6 and 12 and weeks 18 and 24. Prespecified subgroups analyzed were patients with low HDL-C levels and with the metabolic syndrome.

Results: Simvastatin increased HDL-C and apo A-I values significantly more than did atorvastatin for the mean of weeks 6 and 12 (8.9% vs 3.6% and 4.9% vs -0.9%, respectively) and the mean of weeks 18 and 24 (8.3% vs 4.2% and 3.7% vs -1.4%). These differences were observed across both baseline HDL-C subgroups (<40 mg/dL, > or =40 mg/dL) and in patients with the metabolic syndrome. Low-density lipoprotein cholesterol and triglyceride reductions were greater with atorvastatin. Consecutive elevations >3x the upper limit of normal in alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) occurred in significantly fewer patients treated with simvastatin than with atorvastatin (2/453 [0.4%] vs 13/464 [2.8%]), with most elevations observed in women taking atorvastatin (11/209 [5.3%] vs 1/199 [0.5%] for simvastatin).

Conclusions: Simvastatin (80 mg) increased HDL-C and apo A-I significantly more than did atorvastatin (80 mg) in patients with hypercholesterolemia. This advantage was observed regardless of HDL-C level at baseline or the presence of the metabolic syndrome. Significantly fewer consecutive elevations >3x the upper limit of normal in ALT and/or AST occurred in patients receiving simvastatin.

Publication types

  • Clinical Trial
  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Alkaline Phosphatase / metabolism
  • Apolipoprotein A-I / drug effects*
  • Atorvastatin
  • Cholesterol, HDL / drug effects*
  • Diarrhea / chemically induced
  • Double-Blind Method
  • Female
  • Heptanoic Acids / administration & dosage*
  • Heptanoic Acids / adverse effects
  • Humans
  • Hypercholesterolemia / drug therapy*
  • Hypercholesterolemia / metabolism
  • Male
  • Middle Aged
  • Musculoskeletal Diseases / chemically induced
  • Nausea / chemically induced
  • Pyrroles / administration & dosage*
  • Pyrroles / adverse effects
  • Simvastatin / administration & dosage*
  • Simvastatin / adverse effects

Substances

  • Apolipoprotein A-I
  • Cholesterol, HDL
  • Heptanoic Acids
  • Pyrroles
  • Atorvastatin
  • Simvastatin
  • Alkaline Phosphatase