Lipid-altering efficacy of ezetimibe/simvastatin 10/40 mg compared with doubling the statin dose in patients admitted to the hospital for a recent coronary event: the INFORCE study.
BACKGROUND
The aim of this study was to investigate the efficacy and safety profile of switching to ezetimibe/simvastatin (Eze/Simva) 10/40 mg compared with doubling the statin dose upon discharge in patients taking a statin and admitted to the hospital for the investigation of a coronary event.


METHODS
This phase IV, multi-centre, randomised, open-label, active-controlled, parallel group study enrolled 424 patients (aged >/= 18 years) hospitalised for an acute coronary event and taking a stable dose of a statin (>/= 6 weeks) that could be doubled per the product label. Upon discharge from the hospital, patients were stratified by their statin dose/potency (high, medium and low) and randomised 1 : 1 to doubling of the statin dose (n = 211) or Eze/Simva 10/40 mg (n = 213) for 12 weeks. The primary efficacy variable was the absolute low-density lipoprotein cholesterol (LDL-C) value (mmol/l) at study end-point.


RESULTS
Mean baseline LDL-C for the two treatment groups were 2.48 and 2.31 mmol/l for the Eze/Simva and statin groups respectively. At study end-point, least squares mean LDL-C values were 1.74 mmol/l in the Eze/Simva group and 2.22 mmol/l in the statin group resulting in a significant between-group difference of -0.49 mmol/l (p </= 0.001). Eze/Simva 10/40 mg also produced significantly lower total cholesterol (-0.49 mmol/l), non-high-density lipoprotein cholesterol [(non-HDL-C); -0.53 mmol/l] and apolipoprotein B (-0.14 mmol/l) values compared with doubling the statin dose (p </= 0.001 for all). Both treatments produced similar effects on triglycerides, C-reactive protein and HDL-C; the between treatment group differences were not significant (p >/= 0.160). Significantly more patients achieved LDL-C levels < 2.5 (< 100 mg/dl; 86% vs. 72%), < 2.0 (< 77 mg/dl; 70% vs. 42%) and < 1.8 mmol/l (< 70 mg/dl; 60% vs. 31%) with Eze/Simva than statin (all p </= 0.001). Eze/Simva was generally well tolerated, with a safety profile similar to statin. There were no differences in the incidences of liver transaminases >/= 3 x upper limit of normal (ULN) or creatine kinase >/= 10 x ULN between the groups.


CONCLUSIONS
In patients taking a statin and admitted to the hospital for investigation of a coronary event, treatment with Eze/Simva 10/40 mg for 12 weeks produced greater improvements in lipids with a similar safety profile compared with doubling of the statin dose.
Reckless
J P D
JP
Royal United Hospital, Bath, UK. mpsjpdr@bath.ac.uk
Henry
P
P
Pomykaj
T
T
Lim
S T
ST
Massaad
R
R
Vandormael
K
K
Johnson-Levonas
A O
AO
Lis
K
K
Brudi
P
P
Allen
C
C
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000924:Anticholesteremic Agents / Q000008:administration & dosage*; D001384:Azetidines / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D000069438:Ezetimibe; D006760:Hospitalization; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage*; D006937:Hypercholesterolemia / Q000188:drug therapy*; D008875:Middle Aged; D009203:Myocardial Infarction / Q000188:drug therapy*; D019821:Simvastatin / Q000008:administration & dosage*; D016896:Treatment Outcome
D000924:Anticholesteremic Agents; D001384:Azetidines; D004338:Drug Combinations; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D019821:Simvastatin; D000069438:Ezetimibe