Lipid-altering efficacy of ezetimibe ⁄ simvastatin 10⁄40mg compared with doubling the statin dose in patients
admitted to the hospital for a recent coronary event: the INFORCE study
摘要：该研究针对先前采用单一他汀类药物治疗、且近期有过冠脉事件的高风险患者，比较换用较依折麦布/辛伐他汀联合用药与双倍剂量阿托伐他汀的疗效，12周研究结论提示依折麦布/辛伐他汀对高风险患者LDL-C水平及其他多种血脂水平调整疗效明显优于双倍剂量的阿托伐他汀。
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 ofthe 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.
