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).
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.
Ballantyne
Christie M
CM
Baylor College of Medicine, Houston, Tex 77030, USA. cmb@bcm.tmc.edu
Blazing
Michael A
MA
Hunninghake
Donald B
DB
Davidson
Michael H
MH
Yuan
Zhong
Z
DeLucca
Paul
P
Ramsey
Karen E
KE
Hustad
Carolyn M
CM
Palmisano
Joanne
J
D000328:Adult; D000368:Aged; D000469:Alkaline Phosphatase / Q000378:metabolism; D016632:Apolipoprotein A-I / Q000187:drug effects*; D000069059:Atorvastatin; D008076:Cholesterol, HDL / Q000187:drug effects*; D003967:Diarrhea / Q000139:chemically induced; D004311:Double-Blind Method; D005260:Female; D006538:Heptanoic Acids / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D006937:Hypercholesterolemia / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009140:Musculoskeletal Diseases / Q000139:chemically induced; D009325:Nausea / Q000139:chemically induced; D011758:Pyrroles / Q000008:administration & dosage* / Q000009:adverse effects; D019821:Simvastatin / Q000008:administration & dosage* / Q000009:adverse effects
D016632:Apolipoprotein A-I; D008076:Cholesterol, HDL; D006538:Heptanoic Acids; D011758:Pyrroles; D000069059:Atorvastatin; D019821:Simvastatin; D000469:Alkaline Phosphatase