title: Influence of previous statin therapy on cholesterol-lowering effect of ezetimibe.
abstract: OBJECTIVE
  The inhibition of cholesterol absorption by ezetimibe increases cholesterol synthesis. The effect of inhibition of cholesterol synthesis on cholesterol absorption is controversial. The influence of these interactions on cholesterol levels is unknown. We investigated on the extent to which cholesterol levels were affected by the reaction of one pathway to the inhibition of the other pathway.
  
  
  METHODS
  This case-controlled study enrolled 198 patients who needed cholesterol-lowering drugs. Ezetimibe (10 mg) was administered to the patients with (n=58) and without on-going statin therapy (n=58). Simvastatin (20 mg) was administered to the patients treated with (n=41) and without ezetimibe (n=41).
  
  
  RESULTS
  Ezetimibe without statin lowered the total cholesterol by 13.3±8.8% (p<0.001) and the low density lipoprotein-cholesterol (LDL-C) by 18.7±15.3% (p<0.001). Ezetimibe added to statin decreased the total cholesterol by 21.1±7.7% (p<0.001) and the LDL-C by 29.9±12.6% (p<0.001). The total cholesterol and LDL-C were reduced more by ezetimibe in patients with statin therapy than in those without statin therapy (p<0.001 and p<0.001, respectively). The differences in the effect of simvastatin on total cholesterol and LDL-C between the patients with and without ezetimibe showed borderline significance (p=0.10 and p=0.055, respectively).
  
  
  CONCLUSIONS
  A prior inhibition of cholesterol synthesis by statin enhanced the effect of ezetimibe on total cholesterol and LDL-C by 7.8% and 11.2%, respectively. This finding suggests that ezetimibe increased cholesterol synthesis, resulting in a significant elevation of cholesterol levels.
authors.affiliation: Division of Cardiology, Department of Internal Medicine, College of Medicine, Chung-Ang University, Seoul, Korea.
authors.forename: Young Hwan
authors.initials: YH
authors.lastname: Choi
authors.affiliation: Division of Cardiology, Department of Internal Medicine, College of Medicine, Chung-Ang University, Seoul, Korea.
authors.forename: Young
authors.initials: Y
authors.lastname: Kim
authors.affiliation: Division of Cardiology, Department of Internal Medicine, College of Medicine, Chung-Ang University, Seoul, Korea.
authors.forename: Cheol Won
authors.initials: CW
authors.lastname: Hyeon
authors.affiliation: Division of Cardiology, Department of Internal Medicine, College of Medicine, Chung-Ang University, Seoul, Korea.
authors.forename: Seonghyup
authors.initials: S
authors.lastname: Hyun
authors.affiliation: Division of Cardiology, Department of Internal Medicine, College of Medicine, Chung-Ang University, Seoul, Korea.
authors.forename: Jee Eun
authors.initials: JE
authors.lastname: Kwon
authors.affiliation: Division of Cardiology, Department of Internal Medicine, College of Medicine, Chung-Ang University, Seoul, Korea.
authors.forename: Hoyoun
authors.initials: H
authors.lastname: Won
authors.affiliation: Division of Cardiology, Department of Internal Medicine, College of Medicine, Chung-Ang University, Seoul, Korea.
authors.forename: Seung Yong
authors.initials: SY
authors.lastname: Shin
authors.affiliation: Division of Cardiology, Department of Internal Medicine, College of Medicine, Chung-Ang University, Seoul, Korea.
authors.forename: Wang-Soo
authors.initials: WS
authors.lastname: Lee
authors.affiliation: Division of Cardiology, Department of Internal Medicine, College of Medicine, Chung-Ang University, Seoul, Korea.
authors.forename: Kwang Je
authors.initials: KJ
authors.lastname: Lee
authors.affiliation: Division of Cardiology, Department of Internal Medicine, College of Medicine, Chung-Ang University, Seoul, Korea.
authors.forename: Sang-Wook
authors.initials: SW
authors.lastname: Kim
authors.affiliation: Division of Cardiology, Department of Internal Medicine, College of Medicine, Chung-Ang University, Seoul, Korea.
authors.forename: Tae Ho
authors.initials: TH
authors.lastname: Kim
authors.affiliation: Division of Cardiology, Department of Internal Medicine, College of Medicine, Chung-Ang University, Seoul, Korea.
authors.forename: Chee Jeong
authors.initials: CJ
authors.lastname: Kim
keywords: Ezetimibe; Hydroxymethylglutaryl-CoA reductase inhibitors; Lipids; Lipoproteins
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