The effect of simvastatin-ezetimibe combination therapy on adipose tissue hormones and systemic inflammation in patients with isolated hypercholesterolemia. The Effect of HMG-CoA Reductase Inhibitor on Insulin Resistance in Patients Undergoing Peritoneal Dialysis Effects of Combination of Ezetimibe and Rosuvastatin on Coronary Artery Plaque in Patients with Coronary Heart Disease. Comparison of the effects of simvastatin vs. rosuvastatin vs. simvastatin/ezetimibe on parameters of insulin resistance. Effects of 90-day hypolipidemic treatment on insulin resistance, adipokines and proinflammatory cytokines in patients with mixed hyperlipidemia and impaired fasting glucose. Differences in action of atorvastatin and ezetimibe in lowering low-density lipoprotein cholesterol and effect on endothelial function: randomized controlled trial. Improved endothelial function with simvastatin but unchanged insulin sensitivity with simvastatin or ezetimibe. Achieving goal lipid levels with ezetimibe plus statin add-on or switch therapy compared with doubling the statin dose. A pooled analysis. Effect of Ezetimibe and/or Simvastatin on Coenzyme Q10 Levels in Plasma On-treatment analysis of the Improved Reduction of Outcomes: Vytorin Efficacy International Trial (IMPROVE-IT). 2017 Focused Update of the 2016 ACC Expert Consensus Decision Pathway on the Role of Non-Statin Therapies for LDL-Cholesterol Lowering in the Management of Atherosclerotic Cardiovascular Disease Risk: A Report of the American College of Cardiology Task Force on Expert Consensus Decision Pathways. Effects of Rosuvastatin With or Without Ezetimibe on Clinical Outcomes in Patients Undergoing Elective Vascular Surgery Statins as immunomodulators in systemic sclerosis. Efficacy of combination of Ezetimibe 10 mg and rosuvastatin 2.5 mg versus rosuvastatin 5 mg monotherapy for hypercholesterolemia in patients with type 2 diabetes Benefit and tolerability of the coadministration of ezetimibe and atorvastatin in acute coronary syndrome patients. A randomised trial of three counselling strategies for lifestyle changes in patients with hypercholesterolemia treated with ezetimibe on top of statin therapy (TWICE). RESEARCH (Recognized effect of Statin and ezetimibe therapy for achieving LDL-C Goal), a randomized, doctor-oriented, multicenter trial to compare the effects of higher-dose statin versus ezetimibe-plus-statin on the serum LDL-C concentration of Japanese type-2 diabetes patients design and rationale
BACKGROUND Pleiotropic effects of ezetimibe have only been investigated in a few studies . The aim of this article was to compare the effects of simvastatin and the combined treatment with simvastatin and ezetimibe on low- grade systemic inflammation and plasma levels of selected adipokines in patients with isolated hypercholesterolemia . METHODS The study included 69 patients with elevated cholesterol levels , who were allocated to one of the three groups treated for 12 weeks , respectively , with simvastatin ( 40 mg daily ) , simvastatin ( 40 mg daily ) plus ezetimibe ( 10 mg daily ) , or placebo .  Plasma levels of lipids , apolipoproteins , glucose homeostasis markers , leptin , adiponectin , visfatin , tumor necrosis factor-α ( TNF-α ) , free fatty acids ( FFA ) , and high-sensitive C-reactive protein ( hsCRP ) were determined on the allocation day and after 12 weeks of therapy . RESULTS Apart from improving lipid profile , simvastatin administered alone or in combination with ezetimibe , decreased plasma levels of hsCRP , FFA , leptin , visfatin , and TNF-α , as well as increased plasma levels of adiponectin . The combination therapy was superior to simvastatin in influencing plasma lipids/lipoproteins , hsCRP , FFA , and the investigated adipokines . The effect of the combination therapy , but not of simvastatin , on systemic inflammation and plasma adipokines was stronger in insulin-resistant than in insulin-sensitive subjects . CONCLUSIONS The obtained results suggest that insulin-resistant patients with hypercholesterolemia and high cardiovascular risk may benefit the most from the combined treatment with simvastatin and ezetimibe Background Insulin resistance is associated with the progression of atherosclerosis and is reported to predict cardiovascular mortality in patients with end-stage renal disease ( ESRD ) . Although statins exert pleiotropic effects , it is uncertain whether statin therapy improves insulin resistance in these patients . In this prospect i ve r and omized controlled trial , we aim ed to evaluate the effects of statin on insulin resistance among 70 patients undergoing peritoneal dialysis ( PD ) . Methods Patients were r and omized into a statin group ( n = 35 ) or a control group ( n = 35 ) . The statin group received 10 mg per day of rosuvastatin for 6 months . We determined insulin resistance by homeostatic model assessment of insulin resistance ( HOMA-IR ) index . Serum concentrations of adipokines such as adiponectin , leptin , and resistin were measured using enzyme-linked immunosorbent ( ELISA ) assay . As inflammatory markers , high sensitive C-reactive protein ( hsCRP ) and interleukin-6 were also measured . Results There were no significant differences in baseline characteristics between the two groups . Compared to baseline value , statin treatment significantly decreased HOMA-IR index from 2.37 ± 1.08 to 2.05 ± 0.82 ( P = 0.014 ) . There was a concordant decrease in hsCRP levels in the statin group ( 2.05 ± 1.57 to 1.21 ± 0.84 mg/L , P < 0.001 ) , but such improvements were not observed in the control group . When between-group differences in these parameters were compared , hsCRP levels were more decreased in the statin group than in the control group ( P = 0.021 for between-group difference ) , whereas HOMA-IR index was not ( P = 0.189 for between-group difference ) . During this period , statin treatment did not result in the improved adipokine profiles . Conclusion This study showed that statin therapy failed to improve insulin resistance in PD patients despite a significant decline in hsCRP levels after statin treatment . Our finding suggests that reducing inflammation by statin is of limited help to fully attenuate insulin resistance in these patients BACKGROUND In approximately 80 % of cardiovascular disease-related deaths , patients suffer from coronary atherosclerotic heart disease . Ezetimibe is the first intestinal cholesterol absorption inhibitor . Its combination with statins for treating coronary atherosclerotic heart disease has attracted attention worldwide . METHODS The study group comprised 106 patients with coronary atherosclerotic heart disease and hyperlipidaemia . Each was r and omly assigned to one of two groups : ( 1 ) Ezetimibe ( 10 mg , once a night ) plus rosuvastatin ( 10 mg , once a night ) ( n=55 ) or ( 2 ) Rosuvastatin alone ( 10 mg , once a night ) ( n=51 ) . The primary endpoint was new or recurrent myocardial infa rct ion , unstable angina pectoris , cardiac death , and stroke . Blood lipid , high-sensitivity C-reactive protein ( hsCRP ) , interleukin-6 ( IL-6 ) , and matrix metalloproteinase-9 ( MMP-9 ) levels were measured before treatment and at one , six and 12 months after treatment . Coronary plaque size and compositional changes were determined using intravascular ultrasonography . RESULTS The combination of ezetimibe plus rosuvastatin decreased total cholesterol , low-density lipoprotein cholesterol , hsCRP , IL-6 , and MMP-9 levels at six and 12 months after treatment . Statistical significance was detected between two groups . At 12 months , the plaque burden , plaque cross-sectional area , and percentage of necrotic plaque composition were significantly lower in the combination group than in rosuvastatin alone group ( P<0.05 ) . And compared with rosuvastatin alone group , the primary endpoint decreased more effectively in combination group . CONCLUSIONS The combination of ezetimibe and rosuvastatin apparently diminishes lipid levels and plaque burden and improves plaque stability , which may be associated with the potent inhibitory effects of ezetimibe and rosuvastatin on inflammatory cytokines BACKGROUND Statin treatment may be associated with adverse effects on glucose metabolism . Whether this is a class effect is not known . In contrast , ezetimibe monotherapy may beneficially affect insulin sensitivity . OBJECTIVE The aim of this study was to compare the effects of three different regimens of equivalent low-density lipoprotein cholesterol ( LDL-C ) lowering capacity on glucose metabolism . METHODS A total of 153 patients ( 56 men ) , who had not achieved the LDL-C goal recommended by the National Cholesterol Education Program Adult Treatment Panel III ( NCEP-ATP III ) despite a 3-month dietary and lifestyle intervention , were r and omly allocated to receive open-label simvastatin 40 mg or rosuvastatin 10 mg or simvastatin/ezetimibe 10/10 mg for 12 weeks . The primary end point was changes in homeostasis model assessment of insulin resistance ( HOMA-IR ) . Secondary endpoints consisted of changes in fasting insulin levels , fasting plasma glucose ( FPG ) , glycosylated haemoglobin ( HbA(1c ) ) , the HOMA of β-cell function ( HOMA-B ) ( a marker of basal insulin secretion by pancreatic β-cells ) , LDL-C and high sensitivity C reactive protein ( hsCRP ) . RESULTS At week 12 , all three treatment regimens were associated with significant increases in HOMA-IR and fasting insulin levels ( p < 0.05 compared with baseline ) . No significant difference was observed between groups . No change in FPG , HbA(1c ) and HOMA-B levels compared with baseline were noted in any of the three treatment groups . Changes in serum lipids and hsCRP were similar across groups . CONCLUSION To the extent that simvastatin 40 mg , rosuvastatin 10 mg and simvastatin/ezetimibe 10/10 mg are associated with adverse effects on insulin resistance , they appear to be of the same magnitude OBJECTIVE Concerns regarding worsening insulin sensitivity associated with statin treatment have recently emerged . Therefore the aim of this study was to assess and compare the effects of 90-day monotherapies with fenofibrate and atorvastatin , as well as combined therapy , on fasting plasma glucose , insulin resistance index , adipokines ( leptin , resistin , adiponectin ) and levels of proinflammatory cytokines ( TNF-α , IL-6 ) in patients with impaired fasting glucose ( IFG ) and mixed hyperlipidemia . MATERIAL S AND METHODS 67 patients were r and omly assigned to four treatment arms : monotherapy with atorvastatin , monotherapy with fenofibrate , combined therapy ( fenofibrate and torvastatin ) or therapeutic lifestyle change . The study lasted for 90 days . All participants received counseling regarding proper diet and physical activity . RESULTS Compared to the control subjects , prediabetic patients exhibited elevated plasma levels of leptin , resistin , TNF-α and IL-6 , and a lower plasma level of adiponectin . All therapeutic interventions result ed in significant alterations in the lipid profile . Insulin resistance index ( HOMA-IR ) was reduced after treatment with fenofibrate . The effect of atorvastatin on insulin resistance was comparable to therapeutic lifestyle change alone . Therapy with hypolipidemic drugs caused increases in adiponectin levels and decreases in leptin and resistin . An additive effect of the combined treatment on plasma IL-6 level was also observed . CONCLUSIONS Fenofibrate-based treatment was associated with improved insulin sensitivity . Atorvastatin did not cause a deterioration in insulin sensitivity . Hypolipidemic therapies result ed in significant changes in the proinflammatory cytokine network as well as in adipokine levels . At the end of the study the measured parameters nearly resembled those of the healthy subjects BACKGROUND The aim of this study was to compare the effect on endothelial function of increasing statin dose to add-on ezetimibe in patients with coronary artery disease ( CAD ) already treated with statin . METHODS AND RESULTS Two-hundred and forty-three patients with CAD and low-density lipoprotein cholesterol ( LDL-C ) ≥70 mg/dl even after treatment with atorvastatin ( 10 mg ) were prospect ively r and omized to the ezetimibe addition ( 10 mg ) group ( A10E10 ; n=117 ) or to the double atorvastatin dose ( to 20 mg ; A20 ; n=133 ) group for 12 weeks . Primary endpoint was change in endothelial function measured by logarithmic-scale reactive hyperemia index ( L_RHI ) . After treatment , high-sensitivity C-reactive protein ( hs-CRP ) and all lipids except triglyceride and high-density lipoprotein cholesterol were significantly reduced in both groups . The mean percent changes in LDL-C for the A10E10 and A20 groups were -25.8 % and -9.1 % , respectively ( P<0.001 ) . L_RHI increased from 0.47 to 0.62 in the A20 group ( P<0.001 ) , but not in the A10E10 group ( from 0.45 to 0.48 , P=0.399 ) . Absolute change in L_RHI was significantly higher in the A20 than A10E10 group ( 0.02±0.29 vs. 0.16±0.27 , P<0.001 ) . CONCLUSIONS Statin and ezetimibe have different effects on endothelial function independent from LDL-C-lowering effects In addition to their expected effects on lipid profile , lipid-lowering agents may reduce cardiovascular events because of effects on nonclassic risk factors such as insulin resistance and inflammation . Ezetimibe specifically blocks the absorption of dietary and biliary cholesterol as well as plant sterols . Although it is known that an additional reduction of low-density lipoprotein cholesterol ( LDL-C ) levels can be induced by the combination of ezetimibe with statins , it is not known if this can enhance some pleiotropic effects , which may be useful in slowing the atherosclerotic process . This study assessed the effects of simvastatin and ezetimibe , in monotherapy or in combination , on markers of endothelial function and insulin sensitivity . Fifty prediabetic subjects with normo- or mild-to-moderate hypercholesterolemia were r and omly allocated to 2 groups receiving either ezetimibe ( 10 mg/d ) or simvastatin ( 20 mg/d ) for 12 weeks , after which the drugs were combined for both groups for an additional 12-week period . Clinical and laboratory parameters were measured at baseline and after 12 and 24 weeks of therapy . Homeostasis model assessment of insulin resistance index and the area under the curve of insulin were calculated . As expected , both groups receiving drugs in isolation significantly reduced total cholesterol , LDL-C , apolipoprotein B , and triglyceride levels ; and additional reductions were found after the combination period ( P < .05 ) . After 12 weeks of monotherapy , plasminogen activator inhibitor-1 levels and urinary albumin excretion were lower in the simvastatin than in the ezetimibe group . No change in homeostasis model assessment of insulin resistance index , area under the curve of insulin , and adiponectin levels was observed after either the monotherapies or the combined therapy . However , simvastatin combined with ezetimibe provoked significant reductions in E-selectin and intravascular cellular adhesion molecule-1 levels that were independent of LDL-C changes . Our findings support cl aims that simvastatin may be beneficial in preserving endothelial function in prediabetic subjects with normo- or mild-to-moderate hypercholesterolemia . Alternatively , a deleterious effect of ezetimibe on the endothelial function is suggested , considering the increase in intravascular cellular adhesion molecule-1 and E-selectin levels .  Simvastatin and ezetimibe , in isolation or in combination , do not interfere with insulin sensitivity OBJECTIVE Evaluate the lipid-altering effects of ezetimibe added to ongoing statin therapy , statin titration , switching from statin monotherapy to a more potent statin or to ezetimibe/simvastatin . METHODS A pooled analysis of patient-level data from 17 double-blind , active or placebo-controlled studies of 8667 hypercholesterolemic adults r and omized to  ezetimibe 10 mg added to ongoing statins , statin titration ( doubling ) , or switching from ongoing statins to rosuvastatin ( 10 mg ) or to ezetimibe/simvastatin ( 10/20 and 40 mg ) . Percent change from baseline in low-density lipoprotein cholesterol ( LDL-C ) was estimated by analysis of variance . Percent of patients who achieved LDL-C and other guideline -recommended targets , and target lipid levels by baseline distance to goal were evaluated . RESULTS LDL-C percent change from baseline was -26.0 for ezetimibe added to ongoing statin therapy , -27.6 for switching from ongoing statin to ezetimibe/simvastatin , -19.7 for switching to rosuvastatin 10 mg , and -9.7 for dose doubling of the ongoing statin . For patients within 0.8 mmol/L ( 30 mg/dL ) of the target at baseline , LDL-C target attainment rates were 75.9 % for adding ezetimibe to ongoing statin , 72.8 % for switching to ezetimibe/simvastatin , 61.8 % for switching to rosuvastatin , and 44.3 % for statin dose-doubling . Similarly , improvements in other lipids and achievement of non-high-density lipoprotein cholesterol and apolipoprotein B targets among this patient group were largest for ezetimibe added to ongoing statins and switching to ezetimibe/simvastatin ; switching to rosuvastatin 10 mg and statin dose-doubling were less effective . CONCLUSIONS Adding ezetimibe to ongoing statin therapy appeared to be an effective option for patients who do not achieve lipid-lowering goals on statins alone Abstract Background : HMG-CoA reductase inhibitors ( ‘ statins ’ ) have been associated with a decrease in ubidecarenone ( ubiquinone ) levels , a lipophilic enzyme also known as coenzyme Q10 ( CoQ10 ) , due to inhibition of mevalonate synthesis . There is speculation that a decrease in CoQ10 levels may be associated with statin-induced myopathy . The cholesterol absorption inhibitor ezetimibe increases endogenous cholesterol synthesis . The purpose of this study was to examine ( i ) the effects of ezetimibe and simvastatin on plasma CoQ10 levels and ( ii ) whether ezetimibe coadministered with simvastatin abrogates the suggested statin-induced decrease in the CoQ10 plasma levels . Methods : Seventy-two healthy male subjects were enrolled in a single-centre , r and omised , parallel-group study with three arms . Subjects received ezetimibe 10 mg/day , simvastatin 40 mg/day or the combination of ezetimibe 10 mg/day plus simvastatin 40 mg/day for 14 days . Results : Baseline CoQ10 ( 0.99 ± 0.30 mg/L ) levels for the combined groups remained unchanged in the ezetimibe group ( 0.95 ± 0.24 mg/L ) , and significantly decreased in the simvastatin and combination groups ( 0.82 ± 0.18 mg/L , p = 0.0002 and 0.7 ± 0.22 mg/L , p < 0.0001 , respectively ) . There was a correlation between the percentage change in the levels of low-density lipoprotein-cholesterol ( LDL-C ) and the percentage change in CoQ10 levels in all treatment groups ( correlation coefficient [ R ] = 0.67 , p < 0.0001 ) . The ratios of CoQ10 levels to LDL-C levels were significantly increased in all treatment groups ( p < 0.0001 ) . CoQ10 level was independent of cholesterol synthesis or absorption markers . Conclusions : Simvastatin and the combination of simvastatin and ezetimibe significantly decrease plasma CoQ10 levels whereas ezetimibe monotherapy does not . There is a significant correlation between the CoQ10 level decrease and the decrease in total and LDL-C levels in all three treatment groups , suggesting that the CoQ10 decrease may reflect the decrease in the levels of its lipoprotein carriers and might not be statin-specific . The statin-associated CoQ10 reduction is not abrogated through ezetimibe coadministration . Changes of CoQ10 levels are independent of cholesterol synthesis and absorption BACKGROUND We aim ed to determine the efficacy and safety of adding ezetimibe ( Ez ) to simvastatin ( S ) in a post-acute coronary syndrome ( ACS ) population in a prespecified on-treatment analysis . METHODS We evaluated 17,706 post-ACS patients from the IMPROVE-IT trial who had low-density lipoprotein cholesterol values between 50 and 125 mg/dL and who received Ez 10 mg/d with S 40 mg/d ( Ez/S ) or placebo with simvastatin 40 mg/d ( P/S ) . The primary composite end point was cardiovascular death , myocardial infa rct ion , unstable angina , coronary revascularization ≥30 days postr and omization , or stroke . The on-treatment analysis included patients who received study drug for the duration of the trial or experienced a primary end point or noncardiovascular death within 30 days of drug discontinuation . RESULTS Mean low-density lipoprotein cholesterol values at 1 year were 71 mg/dL for P/S and 54 mg/dL for Ez/S ( absolute difference -17 mg/dL = -24 % ; P < .001 ) . The 7-year Kaplan-Meier estimate of the primary end point occurred in 32.4 % in the P/S arm and 29.8 % in the Ez/S arm ( absolute difference 2.6 % ; HRadj 0.92 [ 95 % CI 0.87 - 0.98 ] ; P = .01 ) . The absolute treatment effect favoring Ez/S was 30 % greater than in the intention-to-treat analysis of IMPROVE-IT . CONCLUSIONS This analysis provides additional support for the efficacy and safety of adding Ez to S in this high-risk , post-ACS population In 2016 , the American College of Cardiology published the first expert consensus decision pathway ( ECDP ) on the role of non-statin therapies for low-density lipoprotein (LDL)-cholesterol lowering in the management of atherosclerotic cardiovascular disease ( ASCVD ) risk . Since the publication of that document , additional evidence and perspectives have emerged from r and omized clinical trials and other sources , particularly considering the longer-term efficacy and safety of proprotein convertase subtilisin/kexin 9 ( PCSK9 ) inhibitors in secondary prevention of ASCVD . Most notably , the FOURIER ( Further Cardiovascular Outcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk ) trial and SPIRE-1 and -2 ( Studies of PCSK9 Inhibition and the Reduction of Vascular Events ) , assessing evolocumab and bococizumab , respectively , have published final results of cardiovascular outcomes trials in patients with clinical ASCVD and in a smaller number of high-risk primary prevention patients . In addition , further evidence on the types of patients most likely to benefit from the use of ezetimibe in addition to statin therapy after acute coronary syndrome has been published . Based on results from these important analyses , the ECDP writing committee judged that it would be desirable to provide a focused up date to help guide clinicians more clearly on decision making regarding the use of ezetimibe and PCSK9 inhibitors in patients with clinical ASCVD with or without comorbidities . In the following summary table , changes from the 2016 ECDP to the 2017 ECDP Focused Up date are highlighted , and a brief rationale is provided . The content of the full document has been changed accordingly , with more extensive and detailed guidance regarding decision making provided both in the text and in the up date d algorithms . Revised recommendations are provided for patients with clinical ASCVD with or without comorbidities  on statin therapy for secondary prevention . The ECDP writing committee judged that these new data did not warrant changes to the decision pathways and algorithms regarding the use of ezetimibe or PCSK9 inhibitors in primary prevention patients with LDL-C < 190 mg/dL with or without diabetes mellitus or patients without ASCVD and LDL-C ≥190 mg/dL not due to secondary causes . Based on feedback and further deliberation , the ECDP writing committee down- grade d recommendations regarding bile acid sequestrant use , recommending bile acid sequestrants only as optional secondary agents for consideration in patients intolerant to ezetimibe . For clarification , the writing committee has also included new information on diagnostic categories of heterozygous and homozygous familial hypercholesterolemia , based on clinical criteria with and without genetic testing . Other changes to the original document were kept to a minimum to provide consistent guidance to clinicians , unless there was a compelling reason or new evidence , in which case justification is provided Objective : Cardiovascular complications represent a major cause of morbidity and mortality in patients undergoing vascular surgery . This was a prospect i ve r and omized , open-label study to investigate the effect of lipid-lowering treatment by statin monotherapy or intensified by combining statin with ezetimibe on a 12-month prognosis after vascular surgery . Methods : Patients were r and omly assigned to receive rosuvastatin ( RSV ) 10 mg/d or rosuvastatin 10 mg/d plus ezetemibe ( RSV/EZT ) 10 mg/d , starting prior to scheduled surgical procedure . The primary end point was the first major cardiovascular event , including death from cardiac causes , nonfatal myocardial infa rct ion , ischemic stroke , and unstable angina . Results : A total of 136 patients assigned to RSV and 126 to RSV/EZT completed the study protocol . As many as 6.6 % of patients in the RSV group experience a major cardiovascular event within 30 days after surgery versus 5.6 % in the RSV/EZT group ( P = .72 ) . From month 1 to 12 of the follow-up period , primary end point was observed ( 9 taking RSV vs 2 in the RSV/EZT group [ P = .04 ] ) . Intensified lipid-lowering therapy with RSV/EZT was associated with a greater decrease in low-density lipoprotein cholesterol levels compared with RSV ( 75.87 ± 31.64 vs 87.19 ± 31.7 , P = .004 ) , while no differential effect on triglyceride , high-density lipoprotein cholesterol or high-sensitivity C-reactive protein levels was noted between groups . Conclusion : Our findings indicate that statin therapy intensified by ezetimibe may reduce the incidence of cardiovascular events within the first 12 months after vascular surgery . Nonetheless , whether the use of ezetimibe as an add-on therapy to reduce cardiovascular risk in these patients needs to be tested in larger future studies Systemic sclerosis ( SSc ) has the highest case-specific mortality among the rheumatic diseases . Vascular dysfunction and structural wall abnormalities are among the earliest and fundamental alterations in SSc . Statins have a number of immunomodulating effects on vascular wall cells , which may modify the progression of vascular injury . The aim of this study was to evaluate the potential efficacy of statin therapy in ameliorating endothelial dysfunction ( ED ) in SSc by investigating the effect of statins on some markers that reflect endothelial activation in SSc . Forty patients with SSc were r and omized into two groups to receive 6 months ' treatment with atorvastatin ( n = 20 ; dose , 40 mg/day ) or placebo ( n = 20 ) as an adjuvant to existing therapy . Markers of ED including ET-1 , plasma nitrate levels , and thrombomodulin ( TM ) were evaluated by the enzyme-linked immunosorbent assay ( ELISA ) technique . Fibrinogen , high-sensitivity C-reactive protein ( hsCRP ) , ESR , lipid peroxide ( LP ) , and malonylaldehyde ( MDA ) levels were also assessed . Brachial flow-mediated vasodilatation was assessed by ultrasonography . Patients were studied at base line and after 6 months of statin therapy . After 6 months of therapy , ET-1 , ICAM-1 , sE-selectin , vWF , fibrinogen , ESR , hsCRP as well as LP and MDA levels declined and NO increased significantly in the statin-treated SSc group when compared to the placebo-treated group . Endothelium-dependent vasodilatation ( EDV ) improved significantly in the atorvastatin-treated group . The findings of this study demonstrated statin-mediated improvements in the endothelial function of SSc patients as well as immunomodulating effects . Statins may thus prove to be an invaluable addition to the therapy of the vasculopathy of SSc Background Statins are used to treat hypercholesterolemia in patients with type 2 diabetes mellitus , but many of these patients fail to achieve the target LDL-C level . Recent reports have suggested that a synergistic effect can be obtained by concomitant administration of the cholesterol absorption inhibitor ezetimibe and a statin . However , in patients with type 2 diabetes who are already being treated with satins , it remains unclear whether it is more effective to add ezetimibe or to increase the statin dose . Therefore , this study was performed to examine the effects of these two regimens on LDL-C and lipoproteins . Methods The subjects were type 2 diabetic patients under treatment with rosuvastatin ( 2.5 mg daily ) , who had LDL-C levels ≥80 mg/dL. They were r and omly allocated to a group that received add-on therapy with ezetimibe at 10 mg/day ( combination group , n = 40 ) or an increase of the rosuvastatin dose to 5 mg/day ( dose escalation group , n = 39 ) . These two groups were compared at baseline and after 12 weeks of treatment . Results The percent change of LDL-C was −31 % in the combination group and −12 % in the dose escalation group . Both groups showed a significant decrease , but the decrease was greater in the combination group . In both groups , there was a significant decrease in the levels of small dense LDL-C , oxidized LDL and remnant-like lipoprotein cholesterol . For all of these parameters , the percent changes were greater in the combination group . Only the combination group showed a significant decrease of triglycerides . Multivariate analysis was performed to identify factors associated with reaching an LDL-C level < 80 mg/dL. As a result , add-on therapy with ezetimibe was extracted as a factor related to improvement of LDL-C. Conclusions Compared with increasing the dose of rosuvastatin , the combination of rosuvastatin and ezetimibe not only achieves quantitative but also qualitative improvement of serum lipid levels in type 2 diabetic patients , suggesting that this combination could suppress the progression of atherosclerosis . Trial registration BACKGROUND AND AIM The effect of ezetimibe-statin combination on inflammatory markers in acute coronary syndrome is unknown . The aim of our study is to evaluate the effect of this combination on the lipid profile , the CRP hs and the sCD40 lig and levels in acute coronary syndrome ( ACS ) patients . METHODS This is a r and omized , double-blind study including 93 patients admitted for ACS r and omized in 2 groups ,  ezetimibe 10 mg + atorvastatin 10 mg vs atorvastatin 20 mg + placebo , for 12 weeks follow-up ; blood sample s were collected for lipid profile , ALT , AST , CRP and sCD40L at baseline , 12 hours , 4 weeks , and 12 weeks . RESULTS There was no significant difference in total cholesterol levels , HDL , LDL , CRP , but there was a significant decrease in sCD40L levels in the ezetimibe combination group , with less side effects in the combination group , mainly myalgia ( p = 0.012 ) . CONCLUSION Ezetimibe combination with low dose statin in patients in acute coronary syndrome could be a safe , potent therapy to reduce LDL level with antiinflammatory effect AIMS To compare the impact of three patient counselling strategies for lifestyle changes and to assess the safety and efficacy of ezetimibe on top of statin therapy in hypercholesterolemic high risk patients . METHODS Open , cluster r and omized 3-parallel group trial . Physicians were r and omized between patient motivation on : diet or physical exercise or both . Counselling was adapted to the patient 's baseline Prochaska stage of change . High cardiovascular risk patients , with LDL-C above or equal to 3 mmol/L despite statin therapy for at least 3 months , were enrolled .  Ezetimibe ( 10mg/day ) and patient counselling were started at the same time . Target goal was defined as total cholesterol less than 5 mmol/L and LDL-C above 3 mmol/L. RESULTS Overall 428 physicians enrolled 1,496 patients . At baseline , LDL-C was 3.9+/-0.9 mmol/L and total cholesterol was 6.1+/-1.1 mmol/L. LDL-C decreased by -30.4+/-19.3 % and 869 ( 62 % ) patients achieved target goal . No difference was shown between r and omisation groups . However , improvements in diet consumption patterns were more easily obtained than improvement in physical activity stage of change in non-active patient at baseline . CONCLUSIONS The marked short-term impact ( -30 % ) on LDL-C , although similar between the three groups , slightly exceeds usual LDL-C reductions achieved by this dose of ezetimibe . Decreasing fat consumption seems easier than increasing physical activity . This study confirms the good efficacy , short-term tolerability and safety of ezetimibe on top of statins Aims Hypercholesterolemia coexisting with diabetes still requires clinical intervention to manage the high risk of cardiovascular disease it poses . No second-step strategy is established , however , for cases where strong statins fail to bring cholesterol down to target levels . In this study we seek to demonstrate the superior effect of ezetimibe in combination with strong statins to reduce LDL-C in Japanese patients suffering from both T2DM and hyper LDL-cholesterolemia . Methods T2DM out patients ( 109 patients from 16 institutes ) who failed to achieve the target LDL-C value were recruited and r and omly assigned to two groups , a double-dose-statin group and ezetimibe-plus-statin group . Follow-ups were scheduled at 0 , 12 , 26 , and 52 weeks . The primary endpoint was the percentage change in the level of LDL-C from baseline to 12 weeks . Interim results We could successfully create r and omized ( gender , age , LDL-C , HbA1c , etc . ) two groups except for slight differences in apolipoprotein-B and sd-LDL . Conclusions RESEARCH is the first prospect i ve , parallel-group , multicenter study comparing a double dose of strong statin with ezetimibe plus strong statin for T2DM patients . The RESEARCH study will provide reliable evidence with which to establish a clinical strategy for diabetics who fail to achieve the target LDL-C value
CONCLUSIONS The results suggested that ezetimibe add-on to statin therapy is associated with an enhanced TNF-α-lowering effect  compared with statin monotherapy .
AIMS Statins are known to influence the status of adipokines , which play a key role in the pathophysiology of cardiometabolic diseases .
As the effect of ezetimibe as an add-on to statin therapy on the impact of statins on plasma adipokines levels is currently unclear , the aim of the present study was to investigate this through a meta- analysis of controlled trials .