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

Summary 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. Design:  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 × upper limit of normal (ULN) or creatine kinase ≥ 10 × 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.