Efficacy of ezetimibe in patients with statin-resistant and statin-intolerant familial hyperlipidaemias A comparison of the efficacy of combined ezetimibe and statin therapy with doubling of statin dose in patients with remnant lipoproteinemia on previous statin therapy. Ezetimibe Attenuates Atherosclerosis Associated with Lipid Reduction and Inflammation Inhibition 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 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 Effects of ezetimibe on plasma lipoproteins in severely hypercholesterolemic patients treated with regular LDL-apheresis and statins. Effects of ezetimibe on markers of synthesis and absorption of cholesterol in high-risk patients with elevated C-reactive protein. Consistency of effect of ezetimibe/simvastatin compared with intensified lipid-lowering treatment strategies in obese and non-obese diabetic subjects 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 A community-based, randomized trial of ezetimibe added to statin therapy to attain NCEP ATP III goals for LDL cholesterol in hypercholesterolemic patients: the ezetimibe add-on to statin for effectiveness (EASE) trial. Benefit and tolerability of the coadministration of ezetimibe and atorvastatin in acute coronary syndrome patients. Study of Heart and Renal Protection (SHARP): randomized trial to assess the effects of lowering low-density lipoprotein cholesterol among 9,438 patients with chronic kidney disease. Impact of Dual Lipid-Lowering Strategy With Ezetimibe and Atorvastatin on Coronary Plaque Regression in Patients With Percutaneous Coronary Intervention: The Multicenter Randomized Controlled PRECISE-IVUS Trial. Efficacy and safety of alirocumab in high cardiovascular risk patients with inadequately controlled hypercholesterolaemia on maximally tolerated doses of statins: the ODYSSEY COMBO II randomized controlled trial Effects of Combined Ezetimibe and Simvastatin Therapy as Compared With Simvastatin Alone in Patients With Type 2 Diabetes Treatment with ezetimibe plus low-dose atorvastatin compared with higher-dose atorvastatin alone: is sufficient cholesterol-lowering enough to inhibit platelets?
ABSTRACT Objective : To investigate the efficacy of the cholesterol absorption inhibitor ezetimibe in patients with refractory familial hyperlipidaemia or intolerant to statin therapy . Methods : This prospect i ve study assessed the safety and efficacy of ezetimibe in 200 patients with refractory familial hyperlipidaemias not achieving a low-density-lipoprotein ( LDL ) cholesterol < 3 mmol/L ( 116 mg/dL ) including 22 % intolerant to all statin therapy , many consuming sterol-containing products . Results : Ezetimibe monotherapy result ed in 7 % and 11 % reductions in LDL-cholesterol and apolipoprotein B respectively . Ezetimibe-statin combination therapy  reduced LDL-cholesterol by an additional 11 ± 27 % and apolipoprotein B by 11 ( + 79 to –18)% . There was a similar response between various sub-groups but a wide variation within groups with the greatest effect seen in patients under-responding to statins . The number of patients achieving the LDL‐C target of 3 mmol/L rose from 5.5 % to 18 % . Non-significant effects included a 5 ( + 78 to –470)% reduction in triglycerides , 8 ± 36 % increment in HDL‐cholesterol , 21 ( + 35 to –82)% reduction in C-reactive protein and a 1 ( + 20 to –50)% increase in alanine transaminase . No effects were seen on creatinine , creatine kinase , or insulin resistance . Fourteen patients ( 7 % ) discontinued ezetimibe : seven due to gastrointestinal side-effects , one patient developed an ezetimibe-induced hypercholesterolaemia ( × 1.5 ) , one developed ezetimibe-induced hypertriglyceridaemia ( × 7 ) and five discontinued for other reasons . Conclusion : Ezetimibe is a useful addition to statins in patients with familial hyperlipidaemias but shows a highly variable response profile BACKGROUND AND PURPOSE It remains undetermined whether the addition of ezetimibe to ongoing statin therapy is more effective than increasing the dose of statin for reducing remnant lipoprotein levels in patients with remnant lipoproteinemia on previous statin treatment . This study examined whether combined ezetimibe and statin therapy result ed in a greater improvement in remnant lipoprotein levels and endothelial function than with the dose of statin in patients with remnant lipoproteinemia on previous statin treatment . METHODS AND RESULTS A total of 63 patients with stable coronary artery disease and high levels of remnant-like lipoprotein particle cholesterol ( RLP-C ) ( ≥5.0 mg/dL ) on statin treatment were assigned r and omly to two groups and treated with either addition of ezetimibe ( 10mg/day , n=32 ) or doubling of statin dose ( n=31 ) . The lipid profiles and flow-mediated dilation ( FMD ) of the brachial artery were measured at enrollment and after 6 months of treatment . Statin and ezetimibe combined therapy reduced RLP-C and improved FMD to a greater extent than doubling the statin dose ( % reduction in RLP-C , 48 ± 18 % vs. 33 ± 24 % , respectively , p=0.01 ; % improvement in FMD , 47 ± 48 % vs. 24 ± 23 % , respectively , p=0.02 ) . CONCLUSIONS The addition of ezetimibe to ongoing statin treatment reduced RLP-C levels and improved endothelial dysfunction to a greater extent than doubling the statin dose in patients with high RLP-C levels on previous statin treatment . The present results are preliminary and should be confirmed by further studies on a larger number of study patients Background Ezetimibe , as a cholesterol absorption inhibitor , has been shown protecting against atherosclerosis when combined with statin . However , side by side comparison has not been made to evaluate the beneficial effects of ezetimibe alone versus statin . Herein , the study aim ed to test whether ezetimibe alone would exhibit similar effects as statin and the combination therapy would be necessary in a moderate lesion size . Methods and Results ApoE-/- male mice that were fed a saturated-fat supplemented diet were r and omly assigned to different therapeutic regimens : vehicle , ezetimibe alone ( 10 mg/kg/day ) , atorvastatin ( 20 mg/kg/day ) or combination of ezetimibe and atorvastatin through the drinking water . On 28 days , mice were sacrificed and aorta and sera were collected to analyze the atherosclerotic lesion and blood lipid and cholesterol levels . As a result , ezetimibe alone exerted similar protective effects on atherosclerotic lesion sizes as atorvastatin , which was mediated by lowering serum cholesterol concentrations , inhibiting macrophage accumulation in the lesions and reducing circulatory inflammatory cytokines , such as monocyte chemoattractant protein ( MCP-1 ) and tumor necrosis factor ( TNF-α ) . In contrast to ezetimibe administration , atorvastatin alone attenuated atherosclerotic lesion which is dependent on its anti-inflammation effects . There were no significance differences in lesion areas and serum concentrations of cholesterol , oxidized LDL and inflammatory cytokines between combination therapy and monotherapy ( either ezetimibe or atorvastatin ) . There were significant correlations between the lesion areas and serum concentrations of cholesterol , MCP-1 and TNF-α , respectively . However , there were no significant correlations between the lesion areas and serum concentrations of TGF-β1 and oxLDL . Conclusions Ezetimibe alone played the same protection against a moderate atherosclerotic lesion as atorvastatin , which was associated with lowering serum cholesterol , decreasing circulating inflammatory cytokines , and inhibiting macrophage accumulation in the lesions 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 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 Ezetimibe , a cholesterol absorption inhibitor , can be combined with statins to lower LDL-cholesterol . We evaluated additional ezetimibe ( 10 mg/day ) in a placebo-controlled , double blind , r and omized cross-over study in 20 patients ( age 56+/-9 years , m : f 10:10 , BMI 27.5+/-4.0 kg/m(2 ) ) suffering from severe hypercholesterolemia and CHD who were treated by statins and regular LDL-apheresis .  Lipoproteins ( cholesterol , triglycerides , LDL-cholesterol , HDL-cholesterol , VLDL-cholesterol , VLDL-triglycerides , lipoprotein(a ) ) were determined twice ( before and during ezetimibe/placebo , each given for 5 weeks ) , dietary behaviour was analyzed once ( 3-days- protocol ) during each treatment period . During ezetimibe the mean ( + /-S.D. ) preapheresis LDL-cholesterol concentration decreased from 159+/-26 mg/dl ( 4.11+/-0.67 mmol/l ) to 133+/-28 mg/dl ( 3.44+/-0.72 mmol/l ) ( -16+/-11 % , P<0.0001 , Wilcoxon test ) and the postapheresis LDL-cholesterol from 51+/-9 mg/dl ( 1.32+/-0.23 mmol/l ) to 43+/-8 mg/dl ( 1.11+/-0.21 mmol/l ) ( -14+/-25 % , P<0.05 ) , while there was no significant change during placebo .  Mean VLDL-cholesterol fell by 18+/-71 % ( P<0.05 ) during ezetimibe and was not significantly changed by placebo ( + 19+/-70 % ) . Furthermore , during ezetimibe less plasma volume was treated ( 3725+/-1560 versus 3870+/-1549 ml , P<0.05 ) . Ezetimibe had no effect on pre- and postapheresis triglyceride , HDL-cholesterol and lipoprotein(a ) levels . The effect of ezetimibe was independent of the statin dose . Dietary behaviour did not change and no side effects were observed . Thus , in patients with severe LDL-hypercholesterolemia and CHD the addition of ezetimibe to intensive lipid lowering therapy ( statins and LDL-apheresis ) result ed in a further , clinical ly significant decrease of LDL-cholesterol AIMS High-risk subjects with elevated C-reactive protein ( CRP ) are at high risk for cardiovascular events and frequently require potent statins or combined lipid-lowering therapy to achieve lipid targets and decrease inflammation . Our study aim ed at evaluating the effects of three lipid-modifying therapies on LDL-cholesterol , CRP levels and markers of cholesterol absorption and synthesis . MAIN METHODS A prospect i ve intervention study was performed in high cardiovascular risk individuals receiving atorvastatin 10 mg daily for four weeks . Those with CRP≥2.0mg/L were r and omized to another four-week treatment period with atorvastatin 40 mg , ezetimibe 10 mg or the combination of atorvastatin 40 mg / ezetimibe 10 mg  . Lipids , markers of cholesterol absorption ( campesterol and β-sitosterol ) , and synthesis ( desmosterol ) , as well as CRP were quantified at baseline and end of study . KEY FINDINGS One hundred and twenty two individuals were included .  Atorvastatin alone or combined with ezetimibe  reduced both LDL-cholesterol and CRP ( P<0.002 vs. baseline ; Wilcoxon ) ; ezetimibe did not modify CRP . Ezetimibe-based therapies  reduced absorption markers and their ratios to cholesterol ( P<0.0001 vs. baseline , for all ; Wilcoxon ) , whereas atorvastatin alone increased campesterol/cholesterol and β-sitosterol/cholesterol ratios ( P<0.05 vs. baseline ; Wilcoxon ) . In addition , ezetimibe also increased desmosterol and desmosterol/cholesterol ratio ( P<0.0001 vs. baseline ; Wilcoxon ) . SIGNIFICANCE These results contribute to underst and ing the link between cellular cholesterol homeostasis , inflammation and lipid-modifying therapies . Our findings highlight the broader benefit of combined therapy with a potent statin and ezetimibe  decreasing inflammation , and preventing increase in cholesterol bio synthesis , an effect not observed with ezetimibe alone Purpose This post hoc analysis assessed switching to ezetimibe/simvastatin 10/20 mg vs doubling the baseline statin dose to simvastatin 40 mg or atorvastatin 20 mg or switching to rosuvastatin 10 mg in subgroups of obese ( BMI ≥30 kg/m2 ) and non-obese ( BMI < 30 kg/m2 ) diabetic subjects . Methods This was a r and omized , double-blind , 12-week study of adults 18–79 years with cardiovascular disease with low-density lipoprotein cholesterol ( LDL-C ) ≥70 and ≤160 mg/dl .  Percent change in LDL-C and other lipids was estimated . Results In obese subjects ( n = 466 )  , percent changes in LDL-C and most other lipids were greater with ezetimibe/simvastatin vs doubling the baseline statin dose or switching to rosuvastatin . In non-obese subjects ( n = 342 ) , percent changes in LDL-C , total cholesterol , non-HDL-C , Apo B and Apo A-I were greater with ezetimibe/simvastatin vs doubling the baseline statin dose or switching to rosuvastatin ; and treatment with ezetimibe/simvastatin result ed in greater changes in triglycerides  vs rosuvastatin and HDL-C vs doubling the baseline statin dose . The safety profiles were generally similar . Conclusions Regardless of baseline obesity status , switching to ezetimibe/simvastatin was more effective at reducing LDL-C , total cholesterol , non-HDL-C , and Apo B vs doubling the baseline statin dose to simvastatin 40 mg or atorvastatin 20 mg or switching to rosuvastatin 10 mg 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 OBJECTIVE To determine the extent of reduction in low-density lipoprotein cholesterol ( LDL-C ) level and improvement in National Cholesterol Education Program Adult Treatment Panel III ( NCEP ATP III ) LDL-C goal attainment when ezetimibe was added to ongoing statin therapy in a diverse population of community-based patients . PATIENTS AND METHODS In this multicenter , double-blind , placebo-controlled trial ( from January 2003 to August 2003 ) , hypercholesterolemic patients ( from 299 US primary care and specialty practice s ) with LDL-C levels exceeding NCEP ATP III goals were r and omized ( 2:1 ) to receive  ezetimibe ( 10 mg/d ) or placebo in addition to their ongoing statin therapy for 6 weeks . RESULTS In a study of 3030 r and omized patients , ezetimibe added to statin therapy significantly reduced the LDL-C level by an additional 25.8 % in the total population , compared with an additional 2.7 % reduction with placebo plus statin ( treatment difference , -23.1 % ; P<.001 ) ; the treatment difference ranged from -19.9 % to -24.0 % ( P<.001 ) in each NCEP ATP III risk category subgroup . Significantly ( P<.001 ) more patients ( 71.0 % ) treated with ezetimibe added to statin reached their NCEP ATP III target LDL-C level compared with those treated with placebo plus statin ( 20.6 % ) . The addition of ezetimibe also result ed in improvement in other lipid parameters and high-sensitivity C-reactive protein levels . These benefits were consistent across sex , race , age , statin br and , and dose subgroups . Ezetimibe plus statin therapy was well tolerated , with a safety profile similar to placebo plus statin . CONCLUSION Across multiple subgroups , ezetimibe added to statin therapy consistently produced significant additional improvements in LDL-C levels and goal attainment , as well as in other lipoproteins , compared with addition of placebo . The addition of ezetimibe to statin therapy should be considered for patients not achieving their NCEP ATP III LDL-C goals while receiving statin therapy alone 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 BACKGROUND Lowering low-density lipoprotein ( LDL ) cholesterol with statin therapy has been shown to reduce the incidence of atherosclerotic events in many types of patient , but it remains uncertain whether it is of net benefit among people with chronic kidney disease ( CKD ) . METHODS Patients with advanced CKD ( blood creatinine ≥ 1.7 mg/dL [ ≥ 150 μmol/L ] in men or ≥ 1.5 mg/dL [ ≥ 130 μmol/L ] in women ) with no known history of myocardial infa rct ion or coronary revascularization were r and omized in a ratio of 4:4:1 to ezetimibe 10 mg plus simvastatin 20 mg daily versus matching placebo versus simvastatin 20 mg daily ( with the latter arm rer and omized at 1 year to ezetimibe 10 mg plus simvastatin 20 mg daily vs placebo ) . The key outcome will be major atherosclerotic events , defined as the combination of myocardial infa rct ion , coronary death , ischemic stroke , or any revascularization procedure . RESULTS A total of 9,438 CKD patients were r and omized , of whom 3,056 were on dialysis . Mean age was 61 years , two thirds were male , one fifth had diabetes mellitus , and one sixth had vascular disease . Compared with either placebo or simvastatin alone , allocation to ezetimibe plus simvastatin was not associated with any excess of myopathy , hepatic toxicity , or biliary complications during the first year of follow-up . Compared with placebo , allocation to ezetimibe 10 mg plus simvastatin 20 mg daily yielded average LDL cholesterol differences of 43 mg/dL ( 1.10 mmol/L ) at 1 year and 33 mg/dL ( 0.85 mmol/L ) at 2.5 years . Follow-up is scheduled to continue until August 2010 , when all patients will have been followed for at least 4 years . CONCLUSIONS SHARP should provide evidence about the efficacy and safety of lowering LDL cholesterol with the combination of ezetimibe and simvastatin among a wide range of patients with CKD BACKGROUND Despite st and ard statin therapy , a majority of patients retain a high " residual risk " of cardiovascular events . OBJECTIVES The aim of this study was to evaluate the effects of ezetimibe plus atorvastatin versus atorvastatin monotherapy on the lipid profile and coronary atherosclerosis in Japanese patients who underwent percutaneous coronary intervention ( PCI ) . METHODS This trial was a prospect i ve , r and omized , controlled , multicenter study . Eligible patients who underwent PCI were r and omly assigned to atorvastatin alone or atorvastatin plus ezetimibe ( 10 mg ) daily . Atorvastatin was uptitrated with a treatment goal of low-density lipoprotein cholesterol ( LDL-C ) < 70 mg/dl . Serial volumetric intravascular ultrasound was performed at baseline and again at 9 to 12 months to quantify the coronary plaque response in 202 patients . RESULTS The combination of atorvastatin/ezetimibe result ed in lower levels of LDL-C  than atorvastatin monotherapy ( 63.2 ± 16.3 mg/dl vs. 73.3 ± 20.3 mg/dl ; p < 0.001 ) . For the absolute change in percent atheroma volume ( PAV ) , the mean difference between the 2 groups ( -1.538 % ; 95 % confidence interval [ CI ] : -3.079 % to 0.003 % ) did not exceed the pre-defined noninferiority margin of 3 % , but the absolute change in PAV did show superiority for the dual lipid-lowering strategy ( -1.4 % ; 95 % CI : -3.4 % to -0.1 % vs. -0.3 % ; 95 % CI : -1.9 % to 0.9 % with atorvastatin alone ; p = 0.001 ) . For PAV , a significantly greater percentage of patients who received atorvastatin/ezetimibe  showed coronary plaque regression ( 78 % vs. 58 % ; p = 0.004 ) . Both strategies had acceptable side effect profiles , with a low incidence of laboratory abnormalities and cardiovascular events . CONCLUSIONS Compared with st and ard statin monotherapy , the combination of statin plus ezetimibe showed greater coronary plaque regression , which might be attributed to cholesterol absorption inhibition-induced aggressive lipid lowering . ( Plaque Regression With Cholesterol Absorption Inhibitor or Synthesis Inhibitor Evaluated by Intravascular Ultrasound [ PRECISE-IVUS ] ; NCT01043380 ) Aims To compare the efficacy [ low-density lipoprotein cholesterol ( LDL-C ) lowering ] and safety of alirocumab , a fully human monoclonal antibody to proprotein convertase subtilisin/kexin 9 , compared with ezetimibe , as add-on therapy to maximally tolerated statin therapy in high cardiovascular risk patients with inadequately controlled hypercholesterolaemia . Methods and results COMBO II is a double-blind , double-dummy , active-controlled , parallel-group , 104-week study of alirocumab vs. ezetimibe .  Patients ( n = 720 ) with high cardiovascular risk and elevated LDL-C despite maximal doses of statins were enrolled ( August 2012–May 2013 ) . This pre-specified analysis was conducted after the last patient completed 52 weeks . Patients were r and omized to subcutaneous alirocumab 75 mg every 2 weeks ( plus oral placebo ) or oral ezetimibe 10 mg daily ( plus subcutaneous placebo ) on a background of statin therapy . At Week 24 , mean ± SE reductions in LDL-C from baseline were 50.6 ± 1.4 % for alirocumab vs. 20.7 ± 1.9 % for ezetimibe ( difference 29.8 ± 2.3 % ; P < 0.0001 ) ; 77.0 % of alirocumab and 45.6 % of ezetimibe patients achieved LDL-C < 1.8 mmol/L ( P < 0.0001 ) . Mean achieved LDL-C at Week 24 was 1.3 ± 0.04 mmol/L with alirocumab and 2.1 ± 0.05 mmol/L with ezetimibe , and were maintained to Week 52 . Alirocumab was generally well tolerated , with no evidence of an excess of treatment-emergent adverse events . Conclusion In patients at high cardiovascular risk with inadequately controlled LDL-C , alirocumab achieved significantly greater reductions in LDL-C compared with ezetimibe , with a similar safety profile . Trial registration clinical trials.gov Identifier : NCT01644188 OBJECTIVE To assess the effects of inhibited gastrointestinal cholesterol absorption in statin-treated dyslipidemic patients . RESEARCH DESIGN AND METHODS In a multicenter prospect i ve r and omized double-blind placebo-controlled trial , we primarily compared by ANCOVA the effect of 2-month ezetimibe ( 10 mg/day ) or placebo therapy on LDL cholesterol serum levels in 108 type 2 diabetic patients with albuminuria < 200 μg/min and total cholesterol concentrations > 135 mg/dl despite simvastatin treatment ( 40 mg/day ) . RESULTS Unlike placebo , ezetimibe  decreased LDL cholesterol from 99 ± 31 to 66 ± 22 mg/dl , total cholesterol from 162 ± 36 to 124 ± 30 mg/dl , and apolipoprotein B from 83 ± 22 to 64 ± 18 mg/dl ( P < 0.0001 for all changes versus placebo ) . A total of 72 and 17 % of patients on ezetimibe or placebo  achieved LDL levels < 70 mg/dl , respectively ( P < 0.0001 ) . Treatment was well tolerated . CONCLUSIONS Adding ezetimibe to simvastatin therapy helps to improve the pro-atherogenic lipoprotein profile in type 2 diabetic patients who fail to reach recommended lipid targets with statin therapy alone OBJECTIVES We sought to test the platelet inhibitory and anti-inflammatory effects of a higher statin dosage compared with combined treatment with ezetimibe plus a low statin dose . BACKGROUND Reducing the level of low-density lipoprotein cholesterol ( LDL-C ) with statins induces important pleiotropic effects such as platelet inhibition . An insufficient LDL-C reduction often is treated with ezetimibe , an intestinal cholesterol absorption inhibitor , in combination with a low statin dose . It is not known whether this combination therapy has the same pleiotropic effects as a statin monotherapy . METHODS Fifty-six patients with coronary artery disease were assigned r and omly to receive either 40 mg/day of atorvastatin or 10 mg/day of ezetimibe plus 10 mg/day of atorvastatin for 4 weeks . The levels of LDL-C , platelet activation markers after stimulation , platelet aggregation , and plasma chemokine levels ( i.e. , regulated on activation normally T-cell expressed and secreted [ RANTES ] ) were measured before and after changing lipid-lowering medication . RESULTS Platelet activation markers ( P-selectin ) after stimulation ( adenosine diphosphate ) were reduced by 40 mg/day of atorvastatin ( -5.2 + /- 1.6 arbitrary units ) but not by ezetimibe plus low-dose atorvastatin ( 2.1 + /- 1.8 arbitrary units ; p < 0.005 ) despite a similar reduction of LDL-C  ( atorvastatin -1.01 + /- 0.18 mmol/l vs. ezetimibe plus atorvastatin -1.36 + /- 0.22 mmol/l , p = NS ) . Thrombin receptor-activating peptide-induced platelet aggregation as well as plasma RANTES levels were reduced by 40 mg/day of atorvastatin but not by ezetimibe plus low-dose atorvastatin . CONCLUSIONS Platelet reactivity and a proinflammatory chemokine were reduced more by the higher atorvastatin dose than by ezetimibe plus low-dose atorvastatin . In patients with coronary artery disease , it might be important to combine ezetimibe with higher statin dosages to benefit from cholesterol-independent pleiotropic effects
Conclusions Compared with high-dose statin therapy , ezetimibe with low-dose statin for more than 3 months may have a beneficial tendency of effects on glycemic control
Purpose Given the increased risk of incident diabetes and the side effects on glycemic control with statin treatment , statin and ezetimibe combination therapy has been widely used .
However , whether the same concern exists in ezetimibe remains uncertain .
This meta- analysis aim ed to investigate the influence of ezetimibe treatment on glycemic control .