Differential effects of simvastatin and atorvastatin on high-density lipoprotein cholesterol and apolipoprotein A-I are consistent across hypercholesterolemic patient subgroups.
BACKGROUND
In addition to lowering plasma levels of low-density lipoprotein cholesterol (LDL-C), statins also raise high-density lipoprotein cholesterol (HDL-C).


OBJECTIVE
Recent studies have shown that treatment with simvastatin results in larger increases in HDL-C than those seen with atorvastatin. The results of three clinical studies are analyzed, comparing the effects of simvastatin and atorvastatin on HDL-C and apolipoprotein A-I (apo A-I) in the total cohort and in several subgroups of hypercholesterolemic patients. The three studies were all multicenter, randomized clinical trials that included simvastatin (20-80 mg) and atorvastatin (10-80 mg) treatment arms. The subgroup analyses performed were gender; age (< 65 and > or = 65 years); baseline HDL-C (male: < 40 or > or = 40 mg/dl; female: < 45 or > or = 45 mg/dl), baseline LDL-C (< 160 or > or = 160 mg/dl), and baseline triglycerides (< 200 or > or = 200 mg/dl).


RESULTS
Both drugs produced similar increases in HDL-C levels at low doses; however, at higher drug doses (40 and 80 mg), HDL-C showed a significantly greater increase with simvastatin than with atorvastatin (p < 0.05 to < 0.001). Therefore, while HDL-C remained consistently elevated across all doses of simvastatin, there appeared to be a pattern of decreasing HDL-C with an increasing dose of atorvastatin. A similar negative dose response pattern was also observed with apo A-I in atorvastatin-treated patients, suggesting a reduction in the number of circulating HDL particles at higher doses. Both drugs reduced LDL-C and triglycerides in a dose-dependent fashion, with atorvastatin showing slightly greater effects. The differential effects of atorvastatin and simvastatin on HDL-C and apo A-I were observed for both the whole study cohorts and all subgroups examined; thus, no consistent treatment-by-subgroup interactions were observed.


CONCLUSIONS
The data presented show that, across different hypercholesterolemic patient subgroups, simvastatin increases HDL-C and apo A-I more than atorvastatin at higher doses, with evidence of a negative dose response effect on HDL-C and apo A-I with atorvastatin, but not simvastatin.
Davidson
Michael H
MH
Chicago Center for Clinical Research, Chicago, Illinois 60610, USA. mdavidson@protocare.com
Ose
Leiv
L
Frohlich
Jiri
J
Scott
Russell S
RS
Dujovne
Carlos A
CA
Escobar
Ivan D
ID
Bertolami
Marcelo C
MC
Cihon
Frank
F
Maccubbin
Darbie L
DL
Mercuri
Michele
M
D016632:Apolipoprotein A-I / Q000097:blood*; D000069059:Atorvastatin; D008076:Cholesterol, HDL / Q000097:blood*; D004305:Dose-Response Relationship, Drug; D006538:Heptanoic Acids / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D006937:Hypercholesterolemia / Q000097:blood* / Q000188:drug therapy*; D011758:Pyrroles / Q000494:pharmacology* / Q000627:therapeutic use; D019821:Simvastatin / Q000494:pharmacology* / Q000627:therapeutic use
D016632:Apolipoprotein A-I; D008076:Cholesterol, HDL; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011758:Pyrroles; D000069059:Atorvastatin; D019821:Simvastatin