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

Abstract

Background and ObjectivesThe 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 MethodsThis 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).ResultsEzetimibe 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).ConclusionA 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.

Vascular and metabolic effects of ezetimibe combined with simvastatin in patients with hypercholesterolemia

“…We first reported that unexpectedly, statins dose-dependently significantly reduced adiponectin levels and insulin sensitivity and increased insulin and HbA1c levels despite improvement of endothelium-dependent dilation in hypercholesterolemic patients [7][8][9]16]. By contrast, ezetimibe improved liver steatosis and insulin sensitivity in animal studies [10,11] and significantly improved hepatic steatosis [12] and reduced visceral fat with beneficial effects on adiponectin and insulin resistance in patients with metabolic syndrome [13] and diabetes and insulin resistance [23] although it reduced LDL cholesterol levels further on statins [24].…”

Characteristics and Vascular Complications of Familial Hypercholesterolemia in Korea

“…Although data regarding cardiovascular protection of lipid-lowering therapy in FH is insufficient in Asian countries, a retrospective study in Japan found that CAD onset was delayed in FH patients after the widespread use of statins 46) . In Korea, ezetimibe is known to reduce LDL-C levels by 10% -19% 47,48) and is widely used in FH patients. According to data from the KSLA-supported study, statin -ezetimibe combination is used in about half of all registered patients (unpublished data).…”