Abstract 437: Simvastatin/Ezetimibe 20/10 mg Versus Atorvastatin 20 mg in Patients with Type 2 Diabetes: Results of Single-Center, Randomized Controlled Trial
Ju Hee LeeKyung Woo ParkHyung‐Kwan KimHyun‐Jai ChoEue‐Keun ChoiHyun–Jae KangYong Jin KimBon‐Kwon KooSeil OhHyo‐Soo KimDae-Won SohnByung‐Hee OhYoung-Bae Park
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Introduction Though the efficacy on traditional lipid parameters of simvastatin/ezetimibe and atorvastatin has been studied extensively, ApoB/ApoA1 ratio which has better predictive value for cardiovascular event has not been compared as a primary endpoint in these two treatment groups before, especially in diabetes. Methods This study was a single center, open label, randomized phase 4 study to compare the efficacy and safety of simvastatin/ezetimibe 20/10mg versus atorvastatin 20mg once daily in subjects with type 2 diabetes. One hundred thirty-two well controlled diabetic patients (HbA1C <8.5%) with high LDL cholesterol levels (≥ 100mg/dL) were randomized to two groups. The primary endpoint was the difference in percent change of ApoB/ApoA1 ratio at 12 weeks and secondary endpoints were changes in conventional lipid profiles and apolipoproteins. Results In total, 132 patients (66 for each group; 60 males; mean age, 64.6±7.6 years) were enrolled and 125 patients were included in the full analysis set (62 for simvastatin/ezetimibe; 63 for atorvastatin). Baseline characteristics including lipid profiles were comparable between two groups. After 12 weeks of treatment ApoB/ApoA1 ratio was significantly reduced in both groups, however the differences of % changes between two groups were statistically not significant (-38.1±17.9% vs. -34.2±16.2%, p =0.279) and the changes in conventional lipid profiles including total cholesterol, LDL cholesterol and triglyceride also showed no significant difference. However, HDL cholesterol and ApoA1 levels increased significantly in the simvastatin/ezetimibe group, whereas decreased in the atorvastatin group (HDL cholesterol 4.2±12.7% vs. -0.2±14.8% and ApoA1 2.8±10.0% vs. -1.8±9.8%, p =0.041 and 0.002). In per-protocol analysis, improvement of ApoB/ApoA1 was significantly greater in the simvastatin/ezetimibe group (-42.3±11.9% vs. -36.5±14.1%, p =0.031). The changes of HOMA index and hsCRP were comparable between two groups in full analysis set. But in per-protocol analysis, HOMA index and hsCRP decreased in the simvastatin/ezetimibe group whereas increased in the atorvastatin group although there was no statistic significance. The frequency of adverse reaction was comparable between two groups. Conclusion Based on the results of this randomized controlled trial, simvastatin/ezetimibe 20/10mg might be preferable to atorvastatin 20mg for management of dyslipidemia in the patients with type 2 diabetes.Keywords:
Ezetimibe
Clinical endpoint
Lipid Profile
Introduction: Cardiovascular disease is a major cause of morbidity and mortality throughout the world and hypercholesterolemia is one of the key risk factors. Statins are the first line treatment to reduce atherogenic lipids and there is substantial and robust evidence with atorvastatin for reduction of cardiovascular events and mortality. Ezetimibe can be combined with any dose of atorvastatin for incremental lipid-lowering effects.Areas covered: In this review, the authors summarize the pharmacokinetics, pharmacodynamics and clinical efficacy of the components and the combination of ezetimibe and atorvastatin. Clinical benefits have been seen with ezetimibe combined with simvastatin but studies of its combination with atorvastatin are generally limited to the effects on lipid parameters where the addition of ezetimibe to atorvastatin is generally more effective than titrating the atorvastatin dose.Expert opinion: Although there are no cardiovascular outcomes studies with the combination of ezetimibe and atorvastatin, the greater reduction in atherogenic lipids can be assumed to have greater benefits in reducing cardiovascular events. The ezetimibe–atorvastatin combination is very effective in this respect and well tolerated. Fixed-dose combinations improve medication adherence and this combination should be useful for patients who cannot reach their lipid targets with maximally tolerated statin doses.
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Objective To study the effect of combined simvastatin and ezetimibe on atherosclerosis in ApoE-/- mice on a high-fat diet. Methods Thirty-six male ApoE-/-mice aged 8 weeks were randomly divided into model group, simvastatin treatment group and combined simvastatin and ezetimibe treatment group(12 in each group). Animals in simvastatin treatment group were treated with intragastric simvastatin(20 mg/kg), those in combined simvastatin and ezetimibe treatment group were treated with intragastric simvastatin(20 mg/kg) and ezetimibe(10 mg/kg), and those in model group received PBS buffer, once a day for 8 weeks. Aorta tissue sample taken from the animals were stained with oil red O to measure the area of their plaques. Results The serum TG, TC and LDL-C levels were significantly lower in simvastatin treatment group and combined simvastatin and ezetimibe treatment group than in model group(P0.01). The serum TG and LDL-C levels were significantly lower in combined simvastatin and ezetimibe treatment group than in simvastatin treatment group(P0.01) whereas the HDL-C/ LDL-C ratio was significantly higher in combined simvastatin and ezetimibe treatment group than in model group and simvastatin treatment group(P0.01). The area of plaques was significantly smaller in simvastatin treatment group and combined simvastatin and ezetimibe treatment group than in model group(P0.01). Conclusion Combined simvastatin and ezetimibe inhibits atherosclerosis in ApoE-/- mice more significantly than simvastatin alone.
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Objective:To investigate the efficacy of atorvastatin combined with ezetimibe in the treatment of patients with hypercholesterolemia.Methods:Forty patients(23 males,17 females,aged 58±12 yrs)with severe hypercholesterolemia who failed to achieve lipid lowering target level(LDL-C2.6 mmol/L)after 6 months treatment with atorvastatin(20mg,Qd)were added with ezetimibe(10 mg,Qd)for 3 months observation.Results:After 6 months treatment with atorvastatin,the lipids of TC,LDL-C,TG,ApoB and Lp(a)were decreased and HDL-C elevated remarkably than those at baseline,and with P0.01 respectively.When combined with ezetimibe for 3 months,the lipid level of TC,LDL-C and ApoB was reduced than that of merely using atorvastatin,and with P0.01 in respect.No significant abnormalities were found in particular with AST,ALT and CK during this therapy.Conclusion:Atorvastatin combined with ezetimibe can produce further lipid lowering effects than only atorvastatin in patient with severe hypercholesterolemia.
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OBJECTIVE To observe the therapeutic effectiveness and safty of ezetimibe combined with Simvastatin on patients with hypercholesteremia.METHODS Hypercholesteremia patients were divided into three groups,A(Ezetimibe) group,B(Simvastatin) group,C(combination) group,which were treated with correspond methods.Twelve weeks later patients' plasma level of TC,HDL-C,LDL-C and Apo-B were detected,and the results were analysed.RESULTS:①There was significant difference on of patients in group C be-tween pretherapy and post-treatment(P0.05,P0.01).The difference of average change rates also had statistical significance be-tween patients in three groups(P0.Ol).②There was no relationship between the change level of TC,HDL-C,LDL-C,Apo-B and Simvastatin dosage,in patients of C group.In respect of lowering LDL-C level,Ezetimibe and simvastatin(10 mg/d) was better than Simvastatin(large dosage).The total effective rate of patients in group C was 69.8%,which were higher than that in group A and B(P0.01).The side effects rates had no difference between three groups statistically(P0.05).CONCLUSION The effect of combina-tion of ezetimibe and simvastatin is better than that ezetimibe and simvastatin alone,in regulating cholesterol metabolism,and combination of Ezetimibe and Simvastatin is safe.
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Treatments with ezetimibe/simvastatin (combined or alone) have been indicated as very promising approaches to strongly reduce cholesterol levels in hyperlipidemic patients.We will discuss the efficacy and safety of ezetimibe/simvastatin and their potential to reduce atheroprogression. The molecular mechanisms underlying the possible benefits in atherosclerosis and its complications will also be described.Combined therapy with ezetimibe/simvastatin has been shown to improve lipid profile inducing a very rapid reduction of low-density lipoprotein cholesterol levels in clinical trials. In the near future, potential clinical benefits could be observed in the IMPROVE-IT or SHARP trials. Although clinical studies are needed to further confirm safety of ezetimibe/simvastatin therapy, the greater efficacy in lipid-lowering was not associated with the increase of adverse events. Also the possible association between ezetimibe and cancer, which was observed in the SEAS trial, was not confirmed by further studies and meta-analyses. At present, ezetimibe should be considered an effective lipid-lowering agent that can be used in conjunction with simvastatin at the beginning of therapy, or included in the treatment of patients who do not achieve their low-density lipoprotein cholesterol goal with statins alone.
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Objective To investigate the therapeutic effectiveness and safly of simvastatin combined with ezetimibe on patients with hy-percholesteremia.Methods 71 patients with hypercholesterolemia were divided into the simvatatin group and combination group(simvastatin combined with ezetimibe).which were treated with correspond methods.The therapy lasted for twelve weeks in both two groups.The levels of TC,TG,HDL-C,LDL-C were measured in pre-treatment and post-treatmen.Results After twelve weeks treatment with simvastatin,the lipids of TC、LDL-C、TG were decreased and HDL-C ele-vated remarkably than those at baseline,and with P0.05.When combined with ezetimibe for twelve weeks,the lipid level of TC、LDL-C、TG was reduced than that of merely using simvastatin,and with P0.01 in respect.The side effects rates had no difference between two groups statistically(P0.05).Conclusion The effect of combination of ezetimibe and simvastatin is better than that simvastatin alone,in regulating cholesterol metabolism,and comb-nation of ezetimibe and simvastatin is safe.
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Low doses of ezetimibe/simvastatin provide greater improvements in lipid profile than simvastatin or atorvastatin monotherapy. Ezetimibe/simvastatin may be useful in patients who are unable to tolerate high-dose statin therapy. Combination ezetimibe-simvastatin is less expensive than adding ezetimibe to a statin and more convenient than taking two separate medicines.
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