Influence of Previous Statin Therapy on Cholesterol-Lowering Effect of Ezetimibe

초록

Background and Objectives: 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. Subjects and 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). Conclusion: 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.

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