Effects of ezetimibe coadministered with simvastatin on C-reactive protein in a large cohort of hypercholesterolemic patients

Atherosclerosis. 2005 Apr;179(2):361-7. doi: 10.1016/j.atherosclerosis.2004.10.021. Epub 2004 Dec 15.


Objective: This study assessed the effect of coadministration of ezetimibe and simvastatin on high sensitivity C-reactive protein (hs-CRP) in a large subject cohort (N=1089).

Methods: Data were combined from two nearly identical prospective trials. After dietary stabilization, washout period, and placebo lead-in period, patients with baseline low-density lipoprotein cholesterol (LDL-C) > or =3.75-6.50 mmol/l and triglycerides (TG) < or =4.0 mmol/l were randomized to one of the following daily treatments for 12 weeks: ezetimibe 10 mg; simvastatin monotherapy (10, 20, 40, or 80 mg); ezetimibe 10mg plus simvastatin (10, 20, 40, or 80 mg); or placebo. The primary analysis was the percent change in hs-CRP for the pooled ezetimibe plus simvastatin versus simvastatin monotherapy cohorts.

Results: Ezetimibe coadministered with simvastatin more than doubled the hs-CRP reduction compared to simvastatin monotherapy (-33.3% versus -14.3%, p<0.01). At each individual simvastatin dose level, coadministration therapy exerted significant further incremental hs-CRP reductions compared to simvastatin monotherapy. Similar hs-CRP reductions with coadministered ezetimibe and simvastatin were observed in the major subgroups examined (coronary heart disease, gender, age, baseline LDL-C, and body mass index).

Conclusion: In this large subject cohort, ezetimibe coadministered with simvastatin significantly reduced hs-CRP, suggesting a possible additional anti-inflammatory/anti-atherosclerotic action of combination therapy compared to simvastatin monotherapy.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Anticholesteremic Agents / therapeutic use*
  • Azetidines / therapeutic use*
  • C-Reactive Protein / analysis*
  • C-Reactive Protein / drug effects
  • Cholesterol, LDL
  • Double-Blind Method
  • Drug Administration Schedule
  • Drug Therapy, Combination
  • Ezetimibe
  • Female
  • Humans
  • Hypercholesterolemia / drug therapy*
  • Male
  • Middle Aged
  • Prospective Studies
  • Simvastatin / therapeutic use*


  • Anticholesteremic Agents
  • Azetidines
  • Cholesterol, LDL
  • C-Reactive Protein
  • Simvastatin
  • Ezetimibe