Zetia scientific update |
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Expert Opin Pharmacother. 2008 Aug;9(11):1829-37.
Derdemezis C, Filippatos T, Tselepis A, Mikhailidis D, Elisaf M.
University of Ioannina, Medical School, Department of Internal Medicine, 45110 Ioannina, Greece.
Effects of ezetimibe, either alone or in combination with atorvastatin, on serum visfatin levels: a pilot study.
INTRODUCTION: Ezetimibe inhibits intestinal absorption of cholesterol and lowers circulating low-density lipoprotein cholesterol levels. Visfatin is a novel adipokine, which may be implicated in the atherosclerotic process. OBJECTIVE: The aim of this study was to explore the possible association between ezetimibe administration and serum visfatin concentrations. METHODS: Patients (n = 30) with primary dyslipidemia and another 30 who failed to reach their assigned low-density lipoprotein cholesterol target on atorvastatin therapy (20 mg/day) were included in the study. All participants were given ezetimibe at 10 mg/day for 12 weeks. RESULTS: At baseline the visfatin levels correlated significantly with the total cholesterol (r = 0.61 and p < 0.01) and low-density lipoprotein cholesterol (r = 0.51 and p < 0.01) levels in the statin pretreatment group. Furthermore, in the statin group the post-treatment levels of visfatin and low-density lipoprotein cholesterol were significantly correlated (r = 0.57 and p < 0.01). The serum visfatin concentrations did not change significantly in either the monotherapy or statin pretreatment groups or in subgroups divided according to the baseline lipid variables. In both the ezetimibe monotherapy and ezetimibe plus atorvastatin groups the effect of ezetimibe on the lipid variables depended on the baseline lipid values. The low-density lipoprotein cholesterol:high density lipoprotein cholesterol ratio was consistently improved by ezetimibe in all groups or subgroups. CONCLUSIONS: Ezetimibe did not alter serum visfatin concentrations, either when administered as monotherapy or combined with a statin. Future studies investigating the effect of ezetimibe on visfatin levels need to include groups of patients with distinct lipid characteristics.
J Cardiol. 2008 Aug;52(1):1-6.
Miura S, Saku K.
Department of Cardiology, Fukuoka University School of Medicine, Fukuoka, Japan.
Beneficial effects of ezetimibe-based therapy in patients with dyslipidemia.
Treatment of dyslipidemia is important for the primary and secondary prevention of cardiovascular events. Although statins induce the intensive lowering of low-density lipoprotein (LDL) cholesterol levels, two-thirds of cardiovascular events are not prevented. Ezetimibe has been shown to be a selective inhibitor of the Niemann-Pick C1-like 1 (NPC1L1) transporter of cholesterol across the intestinal wall. Ezetimibe-based therapy may hold the promise of more intensive lowering of LDL cholesterol. This review will address the beneficial effects of ezetimibe in patients with dyslipidemia.
Cardiol J. 2007;14(3):232-7.
Jankowski P, Loster M, Kawecka-Jaszcz K.
Ezetimibe: New perspectives in lipid lowering treatment.
Therapeutic goals for lipid lowering treatment in the prevention of ischemic heart disease are often not reached in clinical practice. Even the highest doses of statins do not guarantee good control of hypercholesterolemia in all patients. Therefore, new lipid lowering drugs are being investigated. One of them is ezetimibe - intestinal cholesterol absorption inhibitor. Treatment with ezetimibe results in significant reduction of total cholesterol and LDL cholesterol levels. It is hoped that concomitant treatment with ezetimibe and other lipid lowering drugs (particularly statins) will be more effective. In large randomized clinical trials, co-administration of ezetimibe with atorvastatin and simvastatin proved to be more effective in lowering cholesterol levels and reaching target therapeutic levels than treatment with statin alone. In addition, combined treatment with ezetimibe and simvastatin was more effective compared to treatment with today's most effectively used statin (rosuvastatin) alone. Reduction of statin dose, due to the combined treatment with ezetimibe, lowers the risk of adverse events. Results of the published studies suggest that ezetimibe is safe and when administered together with statin does not increase the risk of liver or muscle damage. Treatment with ezetimibe may be regarded as a new option in the management of patients who need lipid lowering treatment.
Curr Med Res Opin. 2008 Jul 24.
Fras Z, Mikhailidis AD.
Statin plus ezetimibe treatment in clinical practice: the SI-SPECT (Slovenia (SI) Statin Plus Ezetimibe in Cholesterol Treatment) monitoring of clinical practice study.
BACKGROUND: Poor results from lipid-lowering therapy are mainly due to inadequate dosing and increased adverse effects with high-dose statin monotherapy or drug combinations.OBJECTIVES: The SI-SPECT (Slovenia (SI) Statin Plus Ezetimibe in Cholesterol Treatment) study evaluated the effectiveness of either ezetimibe (EZE) 10 mg as monotherapy or co-administered with on-going statin treatment (S + EZE) in clinical practice.DESIGN AND METHODS: A total of 1053 dyslipidaemic patients (52% men, age 60.3 years, 42.9% with CHD, 32.0% with diabetes mellitus and 69.6% with hypertension) were enrolled. The majority (n = 986; 93.6%) were treated with EZE as 'add-on' to their already prescribed statin, the rest only received EZE (n = 67).MAIN OUTCOME MEASURES: Baseline lipid levels were compared with those obtained 16 weeks after initiating treatment.RESULTS: Total (TC) and low density lipoprotein cholesterol (LDL-C), as well as triglycerides (TG) decreased significantly with S + EZE (by 25.3%, 31.4% and 28.9%, respectively; p < 0.0001 for all comparisons), while monotherapy with EZE resulted in a decrease of 20.8% for TC (p < 0.0001), 28.0% for LDL-C (p < 0.0001) and 28.8% for TG (p = 0.016). At the end of the study 43.9% of patients achieved target TC (< 5.0 mmol/L for primary prevention and < 4.5 mmol/L for secondary prevention), 50.5% target LDL-C (< 3.0 mmol/L for primary prevention and < 2.5 mmol/L for secondary prevention) and 61.6% target TG (< 2.0 mmol/L). The overall incidence of adverse effects during the treatment period, and probably related to EZE use, was low (n = 6, 0.6% of patients).CONCLUSIONS: (1) S + EZE combination therapy was effective and safe irrespective of the statin used, (2) the S + EZE combination resulted in significantly more patients reaching their recommended target lipid levels and (3) the lipid-lowering efficacy of EZE in monotherapy as well as of the S + EZE combination was related to initial lipid values. The much greater decrease of TG than expected could be, at least in part, due to better control/compliance regarding diet and drug treatment during the study and adherence to the need for an overnight fast before sampling.
J Cardiovasc Pharmacol. 2008 Aug;52(2):145-50.
Olijhoek JK, Hajer GR, van der Graaf Y, Dallinga-Thie GM, Visseren FL.
Department of Vascular Medicine, University Medical Centre Utrecht, Utrecht, The Netherlands.
The effects of low-dose simvastatin and ezetimibe compared to high-dose simvastatin alone on post-fat load endothelial function in patients with metabolic syndrome: a randomized double-blind crossover trial.
BACKGROUND AND AIMS: Insulin resistance is associated with postprandial hyperlipidemia and endothelial dysfunction. Patients with metabolic syndrome, characterized by insulin resistance, are at increased cardiovascular risk. The aim of the present study was to investigate whether a similar low-density lipoprotein cholesterol (LDL-c) reduction with combination therapy of low-dose simvastatin and ezetimibe or with high-dose simvastatin alone has similar effects on (post-fat load) endothelial function. METHODS: Randomized, double blind, crossover trial in 19 male obese patients with metabolic syndrome with high-dose simvastatin 80 mg versus combination therapy of low-dose simvastatin 10 mg with ezetimibe 10 mg. Fasting and post-fat load lipids and endothelial function (brachial artery flow-mediated dilation) were determined. RESULTS: Fasting LDL-c concentrations (2.1 +/- 0.5 mmol/L) and fasting endothelial function (6.9 +/- 0.8 vs. 7.6 +/- 1.2%) were the same after both treatments. Although post-fat load plasma triglycerides concentrations were higher (3.2 +/- 0.4 vs. 2.6 +/- 0.2 mmol x h/L) with combination therapy compared to monotherapy, ApoB particles were comparable (0.9 +/- 3.3 vs. -0.2 +/- 2.3 g x h/L). Combination therapy did not decrease post-fat load endothelial function (7.6 +/- 1.2 vs. 7.7 +/- 1.6%), contrary to high-dose simvastatin monotherapy (6.9 +/- 0.8 vs. 4.3 +/- 0.6%). CONCLUSIONS: Combination therapy with low-dose simvastatin and ezetimibe preserved post-fat load endothelial function, contrary to treatment with high-dose simvastatin monotherapy in male metabolic syndrome patients. There were no differences in fasting lipid profiles and endothelial function.
Mol Imaging. 2008 Mar-Apr;7(2):68-76.
Graf K, Dietrich T, Tachezy M, Scholle FD, Licha K, Stawowy P, Grafe M, Hauff P, Fleck E.
Monitoring therapeutical intervention with ezetimibe using targeted near-infrared fluorescence imaging in experimental atherosclerosis.
Ezetimibe (EZE), an inhibitor of cholesterol absorption, reduces atherosclerosis in apolipoprotein E-deficient (apoE(-/-)) mice. The matrix protein ED-B fibronectin (ED-B) is upregulated in atherosclerotic lesions. Using a novel conjugate for near-infrared fluorescence (NIRF) imaging targeting ED-B, we studied the effect of EZE on plaque lesion formation in apoE(-/-) mice. ApoE(-/-) mice received EZE (5 mug/kg/d) or chow up to the age of 4, 6, and 8 months. NIRF imaging of aortic lesions was performed 24 hours after intravenous application ex vivo and in vivo. Plaque lesion formation was analyzed by histology and immunohistochemistry. Aortic lesion formation detected by Sudan staining and NIRF imaging was significantly reduced at 6 and 8 months (p < .001). Plaque areas determined by NIRF imaging significantly correlated with Sudan staining (p < .001). EZE treatment resulted in a significant reduction in plaque macrophage and ED-B immunoreactivity (both p < .05) in brachiocephalic lesions. There was a significant reduction in plaque size in brachiocephalic arteries in 8-month-old mice treated with EZE compared with mice during short-term treatment (p < .05), indicating EZE plaque regression. Targeted NIRF imaging showed a correlation to histologic lesion extension during therapeutical intervention in experimental atherosclerosis.
Drug Dev Ind Pharm. 2008 Aug 8:1-12.
Dixit RP, Nagarsenker MS.
Department of Pharmaceutics, Bombay College of Pharmacy, Kalina, Santacruz (East), Mumbai, India.
Formulation and In Vivo Evaluation of Self-Nanoemulsifying Granules for Oral Delivery of a Combination of Ezetimibe and Simvastatin.
Self-nanoemulsifying granules were formulated with the objective of improving the bioavailability of the ezetimibe and simvastatin when administered together. Composition of self-nanoemulsifying system (SNS) was optimized using various modified oils, surfactant, and cosurfactant mixtures. SNSs were mixed with water and resultant emulsions were characterized for mean globule size and stability. SNSs were adsorbed on hydrophilic colloidal silicon dioxide to give free-flowing self-nanoemulsifying granules. Self-nanoemulsifying granules were characterized by X-ray diffraction pattern, scanning electron microscopy, dissolution profile, and for in vivo performance in hypercholesterolemic rats. X-ray diffraction studies and scanning electron microscopy indicated loss of crystallinity and/or solubilization of both drugs in the self-nanoemulsifying granules. Self-nanoemulsifying granules effected substantial increase in dissolution of the drugs as compared with pure powder of drugs. In vivo evaluation in rats showed significant decrease in the total cholesterol levels and triglyceride levels in rats as compared with positive control confirming potential of self-nanoemulsifying granules as a drug delivery system for the poorly water-soluble drugs.
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Drug category:Antilipemic agents
 Zetia scientific update
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