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 (LDLC) 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. What’s known Previous studies have shown that combined use of ezetimibe and simvastatin, either as co-administration therapy or a single tablet, provides additional low-density lipoprotein reductions beyond that achieved with doubling the statin dose with no increased safety or tolerability risks in high-risk patients with stable coronary heart disease or type 2 diabetes. What’s new This paper presents the results of a study designed to examine the lipid-modifying efficacy and safety of switching to ezetimibe ⁄ simvastatin 10 ⁄40 mg vs. doubling the dose of statin in high-risk patients hospitalised for a recent coronary event. 1