Efficacy of ezetimibe/simvastatin 10/40 mg compared to doubling the dose of low-, medium- and high-potency statin monotherapy in patients with a recent coronary event.
OBJECTIVE
The aim of the study was to compare the efficacy/safety of doubling the dose of low-, medium- and high-potency statins on lipids/lipoproteins versus ezetimibe/simvastatin (EZE/SIMVA) 10/40 mg in patients with a recent coronary event.


METHODS
In this open-label study, patients were stratified by baseline statin therapy (low, medium and high potency) and randomized equally to statin dose doubling or EZE/SIMVA 10/40 mg for 12 weeks. Primary analysis concerned change in low-density lipoprotein cholesterol for the whole population. Treatment-by-stratum interaction evaluated the consistency of treatment effect across statin potency strata. Post hoc analysis of between-group efficacy within strata was performed using ANCOVA.


RESULTS
Within each stratum, EZE/SIMVA produced significantly greater reductions in low-density lipoprotein cholesterol, total cholesterol, apolipoprotein B and non-high-density lipoprotein cholesterol (HDL-C) compared to statin doubling. Numerical trends toward smaller between-group reductions were observed with higher-potency statins and reached statistical significance for apolipoprotein B and non-HDL-C. No significant between-group differences in HDL-C and C-reactive protein were observed within each stratum. EZE/SIMVA produced larger reductions in triglycerides versus low-potency statin, whereas it was similarly effective compared with intermediate-/high-potency statins. The safety/tolerability profiles of the treatments were similar across the strata.


CONCLUSIONS
EZE/SIMVA 10/40 mg produced greater improvements in lipids with a similar safety profile compared to doubling the dose of low-, medium- and high-potency statins.
Brudi
P
P
Merck Schering-Plough, New Jersey, NJ, USA. philippe_brudi@merck.com
Reckless
J P
JP
Henry
D P
DP
Pomykaj
T
T
Lim
S T
ST
Massaad
R
R
Vandormael
K
K
Johnson-Levonas
A O
AO
D000368:Aged; D000789:Angina, Unstable / Q000209:etiology; D000924:Anticholesteremic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001055:Apolipoproteins B / Q000097:blood; D001384:Azetidines / Q000008:administration & dosage* / Q000009:adverse effects; D002097:C-Reactive Protein / Q000378:metabolism; D008076:Cholesterol, HDL / Q000097:blood; D003327:Coronary Disease / Q000209:etiology*; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D000069499:Ezetimibe, Simvastatin Drug Combination; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D006937:Hypercholesterolemia / Q000150:complications* / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D019821:Simvastatin / Q000008:administration & dosage* / Q000009:adverse effects
D000924:Anticholesteremic Agents; D001055:Apolipoproteins B; D001384:Azetidines; D008076:Cholesterol, HDL; D004338:Drug Combinations; D000069499:Ezetimibe, Simvastatin Drug Combination; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D002097:C-Reactive Protein; D019821:Simvastatin