title: The Effect of Aggressive Versus Conventional Lipid-lowering Therapy on Markers of Inflammatory and Oxidative Stress Safety and efficacy of ezetimibe added on to rosuvastatin 5 or 10 mg versus up-titration of rosuvastatin in patients with hypercholesterolemia (the ACTE Study). Hypolipidaemic and anti-inflammatory effects of fixed dose combination of atorvastatin plus ezetimibe in Indian patients with dyslipidaemia. LDL-C goal attainment with the addition of ezetimibe to on-going simvastatin treatment in coronary heart disease patients with hypercholesterolemia Effects of Combined Ezetimibe and Simvastatin Therapy as Compared With Simvastatin Alone in Patients With Type 2 Diabetes Ezetimibe/simvastatin 10/40 mg versus atorvastatin 40 mg in high cardiovascular risk patients with primary hypercholesterolemia: a randomized, double-blind, active-controlled, multicenter study Effects of switching statins on achievement of lipid goals: Measuring Effective Reductions in Cholesterol Using Rosuvastatin Therapy (MERCURY I) study. Combination of direct and indirect evidence in mixed treatment comparisons. 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 Atorvastatin treatment and LDL cholesterol target attainment in patients at very high cardiovascular risk Efficacy and safety of ezetimibe added on to atorvastatin (20 mg) versus uptitration of atorvastatin (to 40 mg) in hypercholesterolemic patients at moderately high risk for coronary heart disease. Comparison of anti-inflammatory effects and high-density lipoprotein cholesterol levels between therapy with quadruple-dose rosuvastatin and rosuvastatin combined with ezetimibe Efficacy and safety of ezetimibe added on to atorvastatin (40 mg) compared with uptitration of atorvastatin (to 80 mg) in hypercholesterolemic patients at high risk of coronary heart disease. Differences in action of atorvastatin and ezetimibe in lowering low-density lipoprotein cholesterol and effect on endothelial function: randomized controlled trial. Safety and efficacy of ezetimibe added to atorvastatin versus up titration of atorvastatin to 40 mg in Patients > or = 65 years of age (from the ZETia in the ELDerly [ZETELD] study). Efficacy and safety of ezetimibe added to atorvastatin versus atorvastatin uptitration or switching to rosuvastatin in patients with primary hypercholesterolemia. Superior benefit of aggressive lipid-lowering therapy for high- risk patients using statins: the SUBARU study--more hypercholesterolemic patients achieve Japan Atherosclerosis Society LDL-C goals with rosuvastatin therapy than with atorvastatin therapy. Achieving lipoprotein goals in patients at high risk with severe hypercholesterolemia: efficacy and safety of ezetimibe co-administered with atorvastatin. Ezetimibe/simvastatin 10/20 mg versus simvastatin 40 mg in coronary heart disease patients. Incremental cholesterol reduction with ezetimibe/simvastatin, atorvastatin and rosuvastatin in UK General Practice (IN-PRACTICE): randomised controlled trial of achievement of Joint British Societies (JBS-2) cholesterol targets. 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. Efficacy of ezetimibe/simvastatin 10/20 and 10/40 mg compared with atorvastatin 20 mg in patients with type 2 diabetes mellitus * Efficacy and safety of ezetimibe co-administered with ongoing atorvastatin therapy in achieving low-density lipoprotein goal in patients with hypercholesterolemia and coronary heart disease. Achieving LDL cholesterol, non-HDL cholesterol, and apolipoprotein B target levels in high-risk patients: Measuring Effective Reductions in Cholesterol Using Rosuvastatin therapY (MERCURY) II. Lipid-altering efficacy of switching from atorvastatin 10 mg/day to ezetimibe/simvastatin 10/20 mg/day compared to doubling the dose of atorvastatin in hypercholesterolaemic patients with atherosclerosis or coronary heart disease. Pleiotropic effects of ezetimibe/simvastatin vs. high dose simvastatin. Achieving goal lipid levels with ezetimibe plus statin add-on or switch therapy compared with doubling the statin dose. A pooled analysis. Effects of ezetimibe on markers of synthesis and absorption of cholesterol in high-risk patients with elevated C-reactive protein. Effect of ezetimibe coadministration with simvastatin in a Middle Eastern population: a prospective, multicentre, randomized, double-blind, placebo-controlled trial
abstract: Purpose Recent trial results are in favor of aggressive lipid lowering using high dose statins in patients needing secondary prevention . It is unclear whether these effects are solely due to more extensive lipid lowering or the result of the potentially anti-inflammatory properties of statins . We aim ed to determine whether aggressive compared with conventional statin therapy is more effective in reducing systemic markers of inflammation and oxidative stress . Material s and methods This was a multi-centre , double-blind , placebo-controlled trial . Patients with previous cardiovascular disease , who did not achieve low density lipoprotein ( LDL ) cholesterol levels < 2.6 mmol/l on conventional statin therapy ( simvastatin 40 mg ) were r and omized to continue with simvastatin 40 mg or to receive atorvastatin 40 mg for 8 weeks and thereafter atorvastatin 80 mg for the final 8 weeks ( aggressive treatment ) . Lipids , C-reactive protein , soluble cellular adhesion molecules , neopterin , von Willebr and Factor , and antibodies against oxidized LDL were measured at baseline and after 16 weeks . Results Lipid levels decreased significantly in the aggressive treatment group ( LDL-C reduction 20.8 % ; P < 0.001 ) , whereas a slight increase was observed in the conventional group ( LDL-C increase 3.7 % ; P = 0.037 ) . A significant reduction in antibodies against oxidized LDL was seen in the aggressive ( 13.4 % ; P < 0.001 ) and the conventional ( 26.8 % ; P < 0.001 ) group , but there was no difference between groups ( P = 0.25 ) . Furthermore , no significant differences in change in other biomarkers was observed between both groups . Conclusions This study does not support the hypothesis that a more profound reduction in inflammatory and oxidative stress contributes to the benefits of aggressive statin therapy The present multicenter , 6-week , r and omized , double-blind , parallel-group , clinical trial evaluated the safety and efficacy of ezetimibe ( 10 mg ) added to stable rosuvastatin therapy versus up-titration of rosuvastatin from 5 to 10 mg or from 10 to 20 mg . The study population included 440 subjects at moderately high/high risk of coronary heart disease with low-density lipoprotein ( LDL ) cholesterol levels higher than the National Cholesterol Education Program Adult Treatment Panel III recommendations ( < 100 mg/dl for moderately high/high-risk subjects without atherosclerotic vascular disease or < 70 mg/dl for high-risk subjects with atherosclerotic vascular disease ) . Pooled data demonstrated that ezetimibe added to stable rosuvastatin 5 mg or 10 mg reduced LDL cholesterol by 21 % . In contrast , doubling rosuvastatin to 10 mg or 20 mg reduced LDL cholesterol by 5.7 % ( between-group difference of 15.2 % , p < 0.001 ) . Individually , ezetimibe plus rosuvastatin 5 mg reduced LDL cholesterol more than did rosuvastatin 10 mg ( 12.3 % difference , p < 0.001 ) , and ezetimibe plus rosuvastatin 10 mg reduced LDL cholesterol more than did rosuvastatin 20 mg ( 17.5 % difference , p < 0.001 ) . Compared to rosuvastatin up-titration , ezetimibe add-on achieved significantly greater attainment of LDL cholesterol levels of < 70 or < 100 mg/dl ( 59.4 % vs 30.9 % , p < 0.001 ) , and < 70 mg/dl in all subjects ( 43.8 % vs 17.5 % , p < 0.001 ) ; produced significantly greater reductions in total cholesterol , non-high-density lipoprotein cholesterol , and apolipoprotein B ( p < 0.001 ) ; and result ed in similar effects on other lipid parameters . Adverse experiences were generally comparable among the groups . In conclusion , compared to up-titration doubling of the rosuvastatin dose , ezetimibe 10 mg added to stable rosuvastatin 5 mg or 10 mg produced greater improvements in many lipid parameters and achieved greater attainment of the National Cholesterol Education Program Adult Treatment Panel III recommended LDL cholesterol targets in subjects with elevated LDL cholesterol and at moderately high/high coronary heart disease risk INTRODUCTION We aim ed to assess the efficacy of fixed dose combination of atorvastatin plus ezetimibe in Indian patients with dyslipidaemia . METHODS A double-blind study was conducted to assess the effect of fixed dose combination of ezetimibe 10 mg plus atorvastatin 10 mg on lipid profile , oxidised low-density lipoprotein ( ox-LDL ) , high-sensitivity C-reactive protein ( hsCRP ) and soluble intercellular cell adhesion molecule ( sICAM ) in dyslipidaemic patients with or at high risk of coronary artery disease , and compare it with atorvastatin 10 mg monotherapy . 30 patients were r and omised to receive ezetimibe plus atorvastatin or atorvastatin once daily for four weeks . RESULTS Of the 30 patients , 10 men and 5 women ( mean age 54.3 ± 1.6 years ) received ezetimibe plus atorvastatin , while 13 men and 2 women ( mean age 53.7 ± 2.8 years ) received only atorvastatin . The combination treatment significantly reduced total cholesterol ( percentage treatment difference -14.4 ± 6.5 , 95 % confidence interval [ CI ] -1.0 to -27.7 ; p = 0.041 ) and LDL cholesterol ( LDL-C ; percentage treatment difference -19.9 ± 6.1 , 95 % CI -7.4 to -32.4 ; p = 0.003 ) compared to atorvastatin monotherapy . 13 patients on combination treament achieved the National Cholesterol Education Program target for LDL-C as compared to 9 patients  on atorvastatin monotherapy ( p = 0.032 ) . Significant reductions in very low-density lipoprotein cholesterol , triglyceride , ox-LDL and sICAM were observed with combination treatment compared to atorvastatin monotherapy . However , no significant change was seen in high-density lipoprotein cholesterol or hsCRP levels between the two groups . CONCLUSION Combination treatment with atorvastatin and ezetimibe had relatively better lipid-lowering and anti-inflammatory efficacy  than atorvastatin monotherapy ABSTRACT Objective : To evaluate the addition of ezetimibe or placebo to on-going simvastatin treatment on attaining the LDL‐C treatment target of ≤ 2.60 mmol/L ( 100 mg/dL ) in coronary heart disease ( CHD ) patients with hypercholesterolemia . Methods : Patients with documented CHD were recruited if they were on a stable dose of simvastatin 10 mg or 20 mg for at least 6 weeks , had LDL‐C > 2.60 mmol/L and ≤ 4.20 mmol/L ( > 100 mg/dL and ≤ 160 mg/dL ) , triglycerides ≤ 4.00 mmol/L ( 355 mg/dL ) and hepatic transaminases and creatine kinase ≤ 50 % above the upper limit of normal . After a 4-week placebo and diet run-in period , eligible patients were r and omized to a double-blind , placebo-controlled comparative study with ezetimibe 10 mg co-administered with on-going simvastatin 10 mg or 20 mg ( n = 208 )  versus placebo to match ezetimibe co-administered with simvastatin 10 mg or 20 mg for 6 weeks ( n = 210 ) . Results : When ezetimibe was added to on-going simvastatin therapy , a significantly greater percentage of patients attained the LDL‐C target of ≤ 2.60 mmol/L after 6 weeks of treatment compared to placebo added to on-going simvastatin ( 80.4 % vs. 17.4 % , respectively ; p ≤ 0.001 ) . When co-administered with on-going simvastatin  therapy , mean percentage reduction in LDL‐C from baseline was significantly larger in the ezetimibe group compared to placebo ( 27.1 % vs. 4.1 % , respectively ; p ≤ 0.001 ) . The co-administration of ezetimibe or placebo to on-going simvastatin treatment was generally well tolerated . Conclusions : Ezetimibe co-administered with on-going simvastatin 10 mg or 20 mg treatment enabled more CHD patients with hypercholesterolemia to attain the LDL‐C treatment target of ≤ 2.60 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 Background A considerable number of patients with severely elevated LDL-C do not achieve recommended treatment targets , despite treatment with statins . Adults at high cardiovascular risk with hypercholesterolemia and LDL-C ≥ 2.59 and ≤ 4.14 mmol/L ( N = 250 ) , pretreated with atorvastatin 20 mg were r and omized to ezetimibe/simvastatin 10/40 mg or atorvastatin 40 mg for 6 weeks . The percent change in LDL-C and other lipids was assessed using a constrained longitudinal data analysis method with terms for treatment , time , time-by-treatment interaction , stratum , and time-by-stratum interaction . Percentage of subjects achieving LDL-C < 1.81 mmol/L , < 2.00 mmol/L , or < 2.59 mmol/L was assessed using a logistic regression model with terms for treatment and stratum . Tolerability was assessed . Results Switching to ezetimibe/simvastatin result ed in significantly greater changes in LDL-C ( -26.81 % vs.-11.81 % ) , total cholesterol ( -15.97 % vs.-7.73 % ) , non-HDL-C ( -22.50 % vs.-10.88 % ) , Apo B ( -17.23 % vs.-9.53 % ) , and Apo A-I ( 2.56 % vs.-2.69 % ) vs. doubling the atorvastatin dose ( all p ≤ 0.002 ) , but not HDL-C , triglycerides , or hs-CRP . Significantly more subjects achieved LDL-C < 1.81 mmol/L ( 29 % vs. 5 % ) , < 2.00 mmol/L ( 38 % vs. 9 % ) or < 2.59 mmol/L ( 69 % vs. 41 % ) after switching to ezetimibe/simvastatin vs. doubling the atorvastatin dose ( all p < 0.001 ) . The overall safety profile appeared generally comparable between treatment groups . Conclusions In high cardiovascular risk subjects with hypercholesterolemia already treated with atorvastatin 20 mg but not at LDL-C < 2.59 mmol/L , switching to combination ezetimibe/simvastatin 10/40 mg provided significantly greater LDL-C lowering and greater achievement of LDL-C targets compared with doubling the atorvastatin dose to 40 mg . Both treatments were generally well-tolerated . Trial registration Registered at clinical trials.gov : BACKGROUND In a multinational trial ( 4522IL/0081 ) , we assessed the effects of switching to low doses of rosuvastatin from commonly used doses of atorvastatin , simvastatin , and pravastatin on low-density lipoprotein cholesterol ( LDL-C ) goal achievement in high-risk patients . METHODS Hypercholesterolemic patients ( n = 3140 ) with coronary heart disease , atherosclerosis , or type 2 diabetes were r and omized to open-label rosuvastatin 10 mg , atorvastatin 10 or 20 mg , simvastatin 20 mg , or pravastatin 40 mg for 8 weeks . Patients either remained on these treatments for another 8 weeks or switched treatments from atorvastatin 10 mg , simvastatin 20 mg , and pravastatin 40 mg to rosuvastatin 10 mg or from atorvastatin 20 mg to rosuvastatin 10 or 20 mg . The primary efficacy measure was the proportion of patients reaching the Joint European Societies ' LDL-C goal ( < 116 mg/dL ) at week 16 . For measures of cholesterol goal achievement , treatment arms were compared using logistic-regression analysis . RESULTS Significant improvement in LDL-C goal achievement was found for patients who switched to rosuvastatin 10 mg , compared with patients who remained on atorvastatin 10 mg ( 86 % vs 80 % , P < .05 ) , simvastatin 20 mg ( 86 % vs 72 % , P < .0001 ) , and pravastatin 40 mg ( 88 % vs 66 % , P < .0001 ) , and between patients switched to rosuvastatin 20 mg and those who remained on atorvastatin 20 mg ( 90 % vs 84 % , P < .01 ) . Similar results were found for achievement of the European combined LDL-C and total cholesterol goals and National Cholesterol Education Program Adult Treatment Panel III LDL-C goals . All statins were well tolerated over 16 weeks . CONCLUSIONS We demonstrated that switching to a more efficacious statin is an effective strategy to improve lipid goal achievement in patients requiring lipid-lowering therapy Mixed treatment comparison ( MTC ) meta- analysis is a generalization of st and ard pairwise meta- analysis for A vs B trials , to data structures that include , for example , A vs B , B vs C , and A vs C trials . There are two roles for MTC : one is to strengthen inference concerning the relative efficacy of two treatments , by including both ' direct ' and ' indirect ' comparisons . The other is to facilitate simultaneous inference regarding all treatments , in order for example to select the best treatment . In this paper , we present a range of Bayesian hierarchical models using the Markov chain Monte Carlo software WinBUGS . These are multivariate r and om effects models that allow for variation in true treatment effects across trials . We consider models where the between-trials variance is homogeneous across treatment comparisons as well as heterogeneous variance models . We also compare models with fixed ( unconstrained ) baseline study effects with models with r and om baselines drawn from a common distribution . These models are applied to an illustrative data set and posterior parameter distributions are compared . We discuss model critique and model selection , illustrating the role of Bayesian deviance analysis , and node-based model criticism . The assumptions underlying the MTC models and their parameterization are also discussed 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 The use of atorvastatin is rapidly increasing among statins since the introduction of generics . However , only limited data are available on its current use and the effectiveness outside of r and omised trials . The aim of the study was to assess low-density lipoprotein ( LDL-C ) levels in ambulatory patients at very high cardiovascular risk on atorvastatin therapy in physician ’s offices . A total of 2625 high-risk patients on atorvastatin were included into this cross-sectional study by 539 office-based physicians between June and December 2014 . 47.0 % of the patients had documented coronary heart disease ( CHD ) , 25.1 % type 2 diabetes mellitus ( DM ) , and 27.9 % CHD plus concomitant DM . The mean age was 66.1 ± 10.8 years , 62.1 % were male . Atorvastatin at the dose of 10 , 20 , 40 and 80 mg/day was administered in 15.6 , 45.7 , 33.9 , and 4.8 % of the patients , respectively . The treatment duration was 92.6 ± 109.6 weeks . The  mean atorvastatin dose at therapy start was 24.8 ± 15.2 mg/day and at time of documentation 27.9 ± 15.8 mg/day . Low-density lipoprotein cholesterol ( LDL-C ) < 70 mg/dL was achieved by 10.5 % of the total cohort ( 7.5 % in DM , 9.3 % in CHD , and 15.2 % in CHD + DM ) . In contrast , according to physicians ’ subjective assessment , 62.7 % of patients ( with small differences between groups ) had reached their individual LDL-C target . In summary , higher doses of atorvastatin are not frequently used in clinical practice . The LDL-C target level < 70 mg/dL as recommended by current guidelines is achieved only in a minority of atorvastatin treated patients at very high cardiovascular risk The aim of this study was to evaluate the efficacy and safety of ezetimibe 10 mg added to atorvastatin 20 mg compared with doubling atorvastatin to 40 mg in patients with hypercholesterolemia at moderately high risk for coronary heart disease who did not reach low-density lipoprotein ( LDL ) cholesterol levels < 100 mg/dl with atorvastatin 20 mg . In this 6-week , multicenter , double-blind , r and omized , parallel-group study , 196 patients treated with atorvastatin 20 mg received atorvastatin 20 mg plus ezetimibe 10 mg or atorvastatin 40 mg for 6 weeks . Adding ezetimibe 10 mg to atorvastatin 20 mg produced significantly greater reductions in LDL cholesterol than increasing atorvastatin to 40 mg ( -31 % vs -11 % , p < 0.001 ) . Significantly greater reductions were also seen in non-high-density lipoprotein cholesterol , total cholesterol , and apolipoprotein B ( p < 0.001 ) . Significantly more patients reached LDL cholesterol levels < 100 mg/dl with atorvastatin 20 mg plus ezetimibe compared with atorvastatin 40 mg ( 84 % vs 49 % , p < 0.001 ) . The 2 treatment groups had comparable results for high-density lipoprotein cholesterol , triglycerides , apolipoprotein A-I , and high-sensitivity C-reactive protein . The incidences of clinical and laboratory adverse experiences were generally similar between groups . In conclusion , the addition of ezetimibe 10 mg to atorvastatin 20 mg was generally well tolerated and result ed in significantly greater lipid-lowering efficacy compared with doubling atorvastatin to 40 mg in patients with hypercholesterolemia at moderately high risk for coronary heart disease Background Statins are frequently administered to reduce low-density lipoprotein cholesterol ( LDL-C ) and vascular inflammation , because LDL-C and high sensitive C-reactive protein ( hs-CRP ) are associated with high risk for cardiovascular events . When statins do not reduce LDL-C to desired levels in high-risk patients with coronary artery disease ( CAD ) , ezetimibe can be added or the statin dose can be increased . However , which strategy is more effective for treating patients with CAD has not been established . The present study compares anti-inflammatory effects and lipid profiles in patients with CAD and similar LDL-C levels who were treated by increasing the statin dose or by adding ezetimibe to the original rosuvastatin dose to determine the optimal treatment for such patients . Methods 46 patients with high-risk CAD and LDL-C and hs-CRP levels of > 70 mg/dL and > 1.0 mg/L , respectively , that were not improved by 4 weeks of rosuvastatin ( 2.5 mg/day ) were r and omly assigned to receive 10 mg ( R10 , n = 24 ) of rosuvastatin or 2.5 mg/day of rosuvastatin combined with 10 mg/day of ezetimibe ( R2.5/E10 , n = 22 ) for 12 weeks . The primary endpoint was a change in hs-CRP . Results Baseline characteristics did not significantly differ between the groups . At 12 weeks , LDL-C and inflammatory markers ( hs-CRP , interleukin-6 , tumour necrosis factor-alpha and pentraxin 3 ) also did not significantly differ between the two groups ( LDL-C : R10 vs. R2.5/E10 : -19.4 ± 14.2 vs. -22.4 ± 14.3 mg/dL ) . However , high-density lipoprotein cholesterol ( HDL-C ) was significantly improved in the R10 , compared with R2.5/E10 group ( 4.6 ± 5.9 vs. 0.0 ± 6.7 mg/dL ; p < 0.05 ) . Conclusion Both enhanced therapies exerted similar anti-inflammatory effects under an equal LDL-C reduction in patients with high-risk CAD despite 2.5 mg/day of rosuvastatin . However , R10 elevated HDL-C more effectively than R2.5/E10.Trial registration The percentage of change from baseline in low-density lipoprotein ( LDL ) cholesterol after the addition of ezetimibe 10 mg to atorvastatin 40 mg was compared with uptitration to atorvastatin 80 mg . In this multicenter , double-blind , parallel-group study , adult hypercholesterolemic patients using atorvastatin 40 mg/day were r and omly assigned to atorvastatin 40 mg plus ezetimibe 10 mg or uptitration to atorvastatin 80 mg . After 6 weeks of treatment , compared with atorvastatin 80 mg , atorvastatin 40 mg plus ezetimibe significantly reduced the primary end point of LDL cholesterol by -27 % versus atorvastatin 80 mg by -11 % ( p < 0.001 ) , as well as significantly reduced non-high-density lipoprotein cholesterol , apolipoprotein B , total cholesterol , and triglycerides significantly more than atorvastatin 80 mg ( all p < 0.001 ) . Percentages of change in high-sensitivity C-reactive protein , high-density lipoprotein cholesterol , and apolipoprotein A-I were similar between groups . Significantly more patients treated with atorvastatin 40 mg plus ezetimibe reached LDL cholesterol < 70 mg/dl versus patients treated with atorvastatin 80 mg ( 74 % vs 32 % ; p < 0.001 ) . Safety and tolerability profiles and incidence of liver and muscle adverse experiences were generally similar between groups . In conclusion , these results showed that adding ezetimibe to atorvastatin 40 mg was significantly more effective than uptitrating to atorvastatin 80 mg at lowering LDL cholesterol and other lipid parameters . Both treatments were generally well tolerated ( clinical trial no. NCT00276484 ) 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 Few clinical studies have focused on the efficacy of lipid-lowering therapies  in patients > or = 65 years of age . The percentage of change from baseline in low-density lipoprotein ( LDL ) cholesterol and the percentage of patients achieving prespecified LDL cholesterol levels after 12 weeks of ezetimibe 10 mg plus atorvastatin versus up titration of atorvastatin were assessed in subjects > or = 65 years old with hyperlipidemia and at high risk of coronary heart disease . After stabilization of atorvastatin 10-mg therapy , 1,053 patients , > or = 65 years old , at high risk of coronary heart disease , with and without atherosclerotic vascular disease and a LDL cholesterol level that was not < 70 or < 100 mg/dl , respectively , were r and omized to receive ezetimibe added to atorvastatin 10 mg for 12 weeks versus up titration to atorvastatin 20 mg for 6 weeks followed by up titration to atorvastatin 40 mg for an additional 6 weeks . Ezetimibe added to atorvastatin 10 mg result ed in significantly greater changes at week 6 in LDL cholesterol ( p < 0.001 ) , significantly more patients with atherosclerotic vascular disease achieving a LDL cholesterol level of < 70 mg/dl ( p < 0.001 ) , and significantly more patients without atherosclerotic vascular disease achieving a LDL cholesterol level of < 100 mg/dl ( p < 0.001 ) at weeks 6 and 12 compared to atorvastatin 20 mg or atorvastatin 40 mg . In addition , ezetimibe plus atorvastatin 10 mg result ed in significantly greater changes at week 6 in total cholesterol , triglycerides , non-high-density lipoprotein ( HDL ) cholesterol , apolipoprotein B ( all p < 0.001 ) , and HDL cholesterol ( p = 0.021 ) compared with atorvastatin 20 mg and significantly greater changes at week 12 in LDL cholesterol , non-HDL cholesterol , apolipoprotein A-I ( p = 0.001 ) , total cholesterol , apolipoprotein B ( p < 0.030 ) , and HDL cholesterol ( p < 0.001 ) compared with atorvastatin 40 mg . Both treatments were generally well tolerated , with comparable safety profiles . In conclusion , adding ezetimibe to atorvastatin 10 mg produced significantly greater favorable changes in most lipids at 6 and 12 weeks and significantly greater attainment of prespecified LDL cholesterol levels than doubling or quadrupling the atorvastatin dose in patients > or = 65 years old at high risk for coronary heart disease Hypercholesterolemic patients ( n = 1,547 ) at high atherosclerotic cardiovascular disease risk with low-density lipoprotein cholesterol ( LDL-C ) levels ≥100 and ≤160 mg/dl while treated with atorvastatin 10 mg/day entered a multicenter , r and omized , double-blind , active-controlled , clinical trial using two 6-week study periods . Period I compared the efficacy/safety of ( 1 ) adding ezetimibe 10 mg ( ezetimibe ) to stable atorvastatin 10 mg , ( 2 ) doubling atorvastatin to 20 mg , or ( 3 ) switching to rosuvastatin 10 mg . Subjects in the latter 2 groups who persisted with elevated LDL-C levels ( ≥100 and ≤160 mg/dl ) after period I , entered period II ; subjects on atorvastatin 20 mg had ezetimibe added to their atorvastatin 20 mg , or uptitrated their atorvastatin to 40 mg ; subjects on rosuvastatin 10 mg switched to atorvastatin 20 mg plus ezetimibe or uptitrated their rosuvastatin to 20 mg . Some subjects on atorvastatin 10 mg plus ezetimibe continued the same treatment into period II . At the end of period I , ezetimibe plus atorvastatin 10 mg reduced LDL-C significantly more than atorvastatin 20 mg or rosuvastatin 10 mg ( 22.2 % vs 9.5 % or 13.0 % , respectively , p < 0.001 ) . At the end of period II , ezetimibe plus atorvastatin 20 mg reduced LDL-C significantly more than atorvastatin 40 mg ( 17.4 % vs 6.9 % , p < 0.001 ) ; switching from rosuvastatin 10 mg to ezetimibe plus atorvastatin 20 mg reduced LDL-C significantly more than uptitrating to rosuvastatin 20 mg ( 17.1 % vs 7.5 % , p < 0.001 ) . Relative to comparative treatments , ezetimibe added to atorvastatin 10 mg ( period I ) or atorvastatin 20 mg ( period II ) produced significantly greater percent attainment of LDL-C targets < 100 or < 70 mg/dl , and significantly greater percent reductions in total cholesterol , non-high-density lipoprotein cholesterol , most lipid and lipoprotein ratios , and apolipoprotein B ( except ezetimibe plus atorvastatin 20 vs atorvastatin 40 mg ) . Reports of adverse experiences were generally similar among groups . In conclusion , treatment of hypercholesterolemic subjects at high cardiovascular risk with ezetimibe added to atorvastatin 10 or 20 mg produced significantly greater improvements in key lipid parameters and significantly greater attainment of LDL-C treatment targets than doubling atorvastatin or switching to ( or doubling ) rosuvastatin at the compared doses AIM There have been few comparisons between rosuvastatin and other statins in Japanese patients . This open-label , r and omized , parallel-group comparative study was performed to compare the efficacy and safety of rosuvastatin ( 5 mg ) and atorvastatin ( 10 mg ) once daily in Japanese patients with hypercholesterolemia . METHODS Patients with hypercholesterolemia who had received atorvastatin ( 10 mg/day ) for at least 4 weeks and were in category B3 , B4 , or C according to the Japan Atherosclerosis Society Guidelines for Diagnosis and Treatment of Atherosclerotic Cardiovascular Diseases 2002 ( JAS2002GL ) were r and omly assigned to rosuvastatin at 5 mg/day ( switched treatment ) or atorvastatin at 10 mg/day ( continued treatment ) . The primary endpoint was the achievement of JAS2002GL LDL-C goals at 8 weeks . RESULTS LDL-C goals were reached by 80.3 % of the rosuvastatin group and 67.3 % of the atorvastatin group at 8 weeks ( p<0.01 ) . The percent change of the LDL-C and LDL-C/HDL-C ratio at 8 weeks was significantly greater in the rosuvastatin group than in the atorvastatin group ( both p<0.01 ) . Furthermore , rosuvastatin improved fasting plasma glucose ( p<0.01 ) . Both drugs were well tolerated . CONCLUSION Rosuvastatin ( 5 mg/day ) is a useful treatment option for high-risk patients with hypercholesterolemia BACKGROUND Despite the efficacy of statins in lowering low-density lipoprotein cholesterol ( LDL-C ) levels , many patients who are at high risk for heart disease with hypercholesterolemia require additional LDL-C level reduction . The cholesterol absorption inhibitor , ezetimibe , has been shown to provide significant incremental reductions in LDL-C levels when co-administered with statins . This study was performed to compare the efficacy and safety of ezetimibe ( 10 mg ) plus response-based atorvastatin titration versus response-based atorvastatin titration alone in the attainment of LDL-C goals in subjects who are at high risk for coronary heart disease ( CHD ) and are not at their LDL-C goal on the starting dose of atorvastatin . METHODS This was a 14-week , multicenter , r and omized , double-blind , active-controlled study conducted in 113 clinical research centers in 21 countries . Participants were adults with heterozygous familial hypercholesterolemia ( HeFH ) , CHD , or multiple ( > or = 2 ) cardiovascular risk factors , and a LDL-C level > or = 130 mg/dL after a 6- to 10-week dietary stabilization and atorvastatin ( 10 mg/day ) open-label run-in period . Eligible subjects continued to receive atorvastatin ( 10 mg ) and were r and omized to receive blinded treatment with ezetimibe ( 10 mg/day ; n = 305 ) or an additional 10 mg/day of atorvastatin ( n = 316 ) . The atorvastatin dose in both groups was doubled after 4 weeks , 9 weeks , or both when the LDL-C level was not at its goal ( < or = 100 mg/dL ) , so that patients receiving combined therapy could reach 40 mg/day and patients receiving atorvastatin alone could reach 80 mg/day . The primary end point was the proportion of subjects achieving their LDL-C level goal at week 14 . A secondary end point was the change in LDL-C level and other lipid parameters at 4 weeks after ezetimibe co-administration with 10 mg/day of atorvastatin versus 20 mg/day of atorvastatin monotherapy . RESULTS The proportion of subjects reaching their target LDL-C level goal of < or = 100 mg/dL was significantly higher in the co-administration group than in the atorvastatin monotherapy group ( 22 % vs 7 % ; P < .01 ) . At 4 weeks , levels of LDL-C , triglycerides , and non-high-density lipoprotein cholesterol were reduced significantly more by combination therapy than by doubling the dose of atorvastatin ( LDL-C -22.8 % versus -8.6 % ; P < .01 ) . The combination regimen had a safety and tolerability profile similar to that of atorvastatin alone . CONCLUSIONS The addition of ezetimibe to the starting dose of 10 mg/day of atorvastatin followed by response-based atorvastatin dose titration to a maximum of 40 mg/day provides a more effective means for reducing LDL-C levels in patients at high risk for CHD than continued doubling of atorvastatin as high as 80 mg/day alone BACKGROUND Reducing low-density lipoprotein cholesterol ( LDL-C ) is the primary goal of therapy in patients with hypercholesterolemia and coronary heart disease ( CHD ) . METHODS This double blind placebo-controlled study enrolled patients 18 to 75 years of age with primary hypercholesterolemia and established CHD who were taking a stable daily dose of simvastatin 20 mg . Patients were r and omized to ezetimibe/simvastatin 10/20 mg ( eze/simva ; n = 56 ) or simvastatin 40 mg ( simva ; n = 56 ) for 6 weeks . Percent change from baseline in LDL-C , total cholesterol , high-density lipoprotein cholesterol ( HDL-C ) , and triglycerides were assessed by use of the Student t test . The percent of patients achieving LDL-C less than 100 mg/dL ( < 2.6 mmol/L ) or less than 80 mg/dL ( < 2.0 mmol/L ) was analyzed via logistic regression with terms for treatment , baseline LDL-C , age , and gender . RESULTS Baseline characteristics were similar between groups . Treatment with eze/simva combination result ed in significantly greater reductions in LDL-C , total cholesterol , and triglycerides versus doubling the dose of simva to 40 mg ( all P < .01 ) . Significantly more patients achieved LDL-C less than 100 mg/dL ( < 2.6 mmol/L ) and less than 80 mg/dL ( < 2.0 mmol/L ) with ezetimibe/simvastatin versus doubling the dose of simva to 40 mg ( 73.2 % vs 25.0 % ; P < .001 ) for simvastatin .  Changes in HDL-C were similar between treatments . Both treatments were generally well tolerated . CONCLUSION In high-risk CHD patients with hypercholesterolemia , treatment with eze/simva combination result ed in significantly greater reductions in LDL-C , total cholesterol and triglycerides , as well as greater achievement of recommended LDL-C targets , compared with doubling the simvastatin dose to 40 mg over the 6-week period . ( CLINICAL TRIAL REGISTRATION NUMBER NCT00423579 ) AIM The aim of this study was to compare ezetimibe/simvastatin combination therapy with intensified statin monotherapy as alternative treatment strategies to achieve the Joint British Societies (JBS)-2 and National Institute for Health and Clinical Excellence low-density-lipoprotein cholesterol ( LDL-C ) target of < 2 mmol/l for secondary prevention or JBS-2 LDL-C target of < 2 mmol/l for primary prevention in high-risk patients who have failed to reach target with simvastatin 40 mg . METHODS This is a prospect i ve , double-blind study conducted in 34 UK primary care centres ; 1748 patients with established cardiovascular disease ( CVD ) , diabetes or high risk of CVD who had been taking simvastatin 40 mg for > or = 6 weeks were screened and 786 ( 45 % ) with fasting LDL-C > or = 2.0 mmol/l ( and < 4.2 mmol/l ) at screening and after a further 6-week run-in period on simvastatin 40 mg were r and omised to ezetimibe/simvastatin 10/40 mg ( as a combination tablet ; n = 261 ) , atorvastatin 40 mg ( n = 263 ) or rosuvastatin 5 mg ( n = 73 ) or 10 mg ( n = 189 ) once daily for 6 weeks . Rosuvastatin dose was based on UK prescribing instructions . The primary outcome measure was the proportion of patients achieving LDL-C < 2 mmol/l at the end of the study . RESULTS The percentage of patients ( adjusted for baseline differences ) achieving LDL-C < 2 mmol/l was 69.4 % with ezetimibe/simvastatin 10/40 mg , compared with 33.5 % for atorvastatin 40 mg [ odds ratio 4.5 ( 95 % CI : 3.0 - 6.8 ) ; p < 0.001 ] and 14.3 % for rosuvastatin 5 or 10 mg [ odds ratio 13.6 ( 95 % CI : 8.6 - 21.6 ) ; p < 0.001 ] . Similar results were observed for achievement of total cholesterol < 4.0 mmol/l . All study treatments were well tolerated . CONCLUSION Approximately 45 % of patients screened had not achieved LDL-C < 2 mmol/l after > or = 12 weeks of treatment with simvastatin 40 mg . In this group , treatment with ezetimibe/simvastatin 10/40 mg achieved target LDL-C levels in a significantly higher proportion of patients during a 6-week period than switching to either atorvastatin 40 mg or rosuvastatin 5 - 10 mg 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 Aim : This r and omized , double‐blind study evaluated the efficacy of switching from atorvastatin ( ATV ) 10 mg to ezetimibe/simvastatin ( EZE/SIMVA ) 10/20 mg , EZE/SIMVA 10/40 mg or doubling the dose of ATV from 10 to 20 mg in patients with type 2 diabetes ( T2D ) This r and omised , double-blind , placebo (PBO)-controlled study evaluated the efficacy and safety of ezetimibe ( EZE ) co-administered with ongoing atorvastatin ( ATV ) therapy in 450 hypercholesterolemic patients with coronary heart disease ( CHD ) who had not achieved their low-density lipoprotein cholesterol ( LDL-C ) goal < or = 2.60 mmol/l while on a stable dose of ATV 10 or 20 mg/day for > or = 6 weeks . After a 4-week diet/baseline active run-in period , patients with LDL-C > 2.60 mmol/l and < or = 4.20 mmol/l were stratified by ATV dose and r and omised ( 1 : 1 ) to EZE 10 mg or PBO for 6 weeks while continuing open-label ATV . Significantly more patients achieved an LDL-C goal < or = 2.6 mmol/l with EZE than PBO ( 81.3 vs. 21.8 % ; p < or = 0.001 ) . Compared to PBO , co-administration of EZE with ongoing ATV led to significantly ( p < or = 0.001 ) greater reductions in LDL-C , total cholesterol , triglycerides , non-high-density lipoprotein cholesterol ( non-HDL-C ) , and apolipoprotein B ; HDL-C was significantly ( p < or = 0.05 ) increased . Co-administration of EZE and ATV was well tolerated , with an overall safety profile similar to ATV alone BACKGROUND National Cholesterol Education Program Adult Treatment Panel III guidelines for patients at a high risk of coronary heart disease set a low-density lipoprotein cholesterol ( LDL-C ) target of < 100 mg/dL. This target can be difficult to attain with diet and current therapy . METHODS In a 16-week multinational trial , 1993 high-risk patients were r and omized to rosuvastatin 20 mg , atorvastatin 10 mg , atorvastatin 20 mg , simvastatin 20 mg , or simvastatin 40 mg for 8 weeks . Patients either remained on starting treatment or switched to lower or milligram-equivalent doses of rosuvastatin for 8 more weeks . RESULTS At 16 weeks , more patients achieved their LDL-C target by switching to rosuvastatin 10 mg than staying on atorvastatin 10 mg ( 66 % vs 42 % , P < .001 ) or simvastatin 20 mg ( 73 % vs 32 % , P < .001 ) . Changing to rosuvastatin 20 mg brought more patients to their LDL-C target than staying on atorvastatin 20 mg ( 79 % vs 64 % , P < .001 ) or simvastatin 40 mg ( 84 % vs 56 % , P < .001 ) . More very high risk patients achieved an LDL-C target of < 70 mg/dL when changed to rosuvastatin from atorvastatin or simvastatin ( within-arm comparisons P < .01 ) . More hypertriglyceridemic patients ( triglycerides > or = 200 mg/dL ) met LDL-C , non-high-density lipoprotein cholesterol ( non-HDL-C ) , and apolipoprotein B targets by changing to rosuvastatin . Switching to rosuvastatin produced greater reductions in LDL-C , total cholesterol , non-HDL-C , apolipoprotein B , and lipid ratios . All treatments were well tolerated , with no differences among treatment groups in skeletal muscle , hepatic , or renal toxicity . CONCLUSION Rosuvastatin 10 or 20 mg is an effective and safe therapeutic option for high-risk patients to achieve their lipid and apolipoprotein targets This r and omised , double-blind study evaluated the efficacy and safety of ezetimibe/simvastatin ( EZE/SIMVA ) 10/20 mg tablet compared to doubling the atorvastatin ( ATV ) dose in hypercholesterolaemic patients with atherosclerotic or coronary heart disease ( CHD ) . The study group included 435 male and female CHD patients ( aged > or=18 years ) who had not achieved their low-density lipoprotein cholesterol ( LDL-C ) goal of < 2.50 mmol/l while on a stable dose of ATV 10 mg for > or=6 weeks . After a 1-week diet/stabilisation period , patients with LDL-C > or=2.50 mmol/l and < or=4.20 mmol/l were r and omised ( 1:1 ) to EZE/SIMVA 10/20 mg/day ( n = 221 ) or ATV 20 mg/day ( n = 214 ) for 6 weeks . The primary efficacy objective was to determine the per cent reduction from baseline in LDL-C at week 6 . EZE/SIMVA 10/20 mg produced significantly greater mean per cent changes from baseline in LDL-C compared with ATV 20 mg ( -32.8 vs. -20.3 % ; p < /= 0.001 ) . A significantly greater proportion of patients achieved an LDL-C goal < 2.50 mmol/l with EZE/SIMVA than ATV ( 77.9 vs. 51.9 % ; p < or= 0.001 ) . Significant improvements in total cholesterol ( -20.3 vs. -13.0 % ) , non-high-density lipoprotein cholesterol ( non-HDL-C ) ( -27.9 vs. -17.0 % ) , apolipoprotein B ( -23.4 vs. -14.7 % ) and HDL-C ( 1.8 vs. -0.4 % ) were observed after switching to EZE/SIMVA 10/20 mg for 6 weeks ( p < 0.05 for all parameters ) . EZE/SIMVA 10/20 mg was generally well tolerated , with an overall safety profile similar to that of ATV 20 mg . EZE/SIMVA 10/20 mg produced superior lipid-altering efficacy by dual inhibition of cholesterol synthesis and intestinal absorption compared with doubling the dose of ATV from 10 to 20 mg BACKGROUND In the setting of stable coronary artery disease ( CAD ) , it is not known if the pleiotropic effects of cholesterol reduction differ between combined ezetimibe/simvastatin and high-dose simvastatin alone . OBJECTIVE We sought to compare the anti-inflammatory and antiplatelet effects of ezetimibe 10mg/simvastatin 20 mg ( E10/S20 ) with simvastatin 80 mg ( S80 ) . METHODS AND RESULTS CAD patients ( n=83 , 63 ± 9 years , 57 % men ) receiving S20 , were r and omly allocated to receive E10/S20 or S80 , for 6 weeks . Lipids , inflammatory markers ( C-reactive protein , interleukin-6 , monocyte chemoattractant protein-1 , soluble CD40 lig and and oxidized LDL ) , and platelet aggregation ( platelet function analyzer [PFA]-100 ) changes were determined . Baseline lipids , inflammatory markers and PFA-100 were similar between groups . After treatment , E10/S20 and S80 patients presented , respectively : ( 1 ) similar reduction in LDL-C ( 29 ± 13 % vs. 28 ± 30 % , p=0.46 ) , apo-B ( 18 ± 17 % vs. 22 ± 15 % , p=0.22 ) and oxidized LDL ( 15 ± 33 % vs. 18 ± 47 % , p=0.30 ) ; ( 2 ) no changes in inflammatory markers ; and , ( 3 ) a higher increase of the PFA-100 with E10/S20 than with S80 ( 27 ± 43 % vs. 8 ± 33 % , p=0.02 ) . CONCLUSIONS These data suggest that among stable CAD patients treated with S20 , ( 1 ) both E10/S20 and S80 were equally effective in further reducing LDL-C ; ( 2 ) neither treatment had any further significant anti-inflammatory effects ; and ( 3 ) E10/S20 was more effective than S80 in inhibiting platelet aggregation . Thus , despite similar lipid lowering and doses 4 × less of simvastatin , E10/S20 induced a greater platelet inhibitory effect than S80 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 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 Objectives To assess the efficacy and safety of ezetimibe coadministered with simvastatin in patients with primary hypercholesterolaemia and coronary artery disease ( CAD ) . Design and setting Prospect i ve , multicentre , r and omized , double-blind , placebo-controlled trial conducted in three Middle Eastern countries . Patients Patients with known CAD , who were being treated with simvastatin 20 mg and had low-density lipoprotein cholesterol ( LDL-C ) concentrations of 2.6 to 4.1 mmol/l , were r and omized to receive daily coadministration of  ezetimibe 10 mg  or placebo . Main outcome measures The primary outcome was percentage reduction of LDL-C after 6 weeks of r and omization . Secondary endpoints included number of patients who achieved National Cholesterol Education Program Adult Treatment Panel III ( NCEP ATP III ) LDL-C level and safety and tolerability . Results We enrolled 144 patients of whom 120 had blood available for final analysis . The coadministration of ezetimibe with ongoing simvastatin therapy result ed in a statistically significant additional reduction in LDL-C concentration as compared with simvastatin monotherapy ( −26.7 versus −9.1 % , respectively ; total additional reduction of 17.6 % , P < 0.0001 ) . More patients in the ezetimibe and simvastatin group achieved NCEP ATP III LDL-C target levels than in the simvastatin monotherapy group ( 70 versus 33 % , respectively ; P = 0.0001 ) . The coadministration of ezetimibe with simvastatin was well tolerated with a safety profile similar to that of simvastatin monotherapy . Conclusion When coadministered with simvastatin therapy , ezetimibe result ed in significant additional reduction in LDL-C and enabled more patients to achieve NCEP ATP III LDL-C target levels . This was achieved safely and with excellent tolerability
target: Similar trends were observed for changes in total cholesterol .
  Implication sGiven the available data , the addition of ezetimibe to ongoing simvastatin , atorvastatin , or rosuvastatin monotherapy offers greater reduction in LDL-C among patients at high risk of CVD compared to doubling the initial statin dose
background: Purpose While statins are used as first-line treatments for high-risk patients with hypercholesterolemia , statin monotherapy is often insufficient to achieve target low-density lipoprotein cholesterol ( LDL-C ) levels .
  Second-line treatment options include up-titration of statin dose , switching to a more potent statin , or combination therapy , e.g. , with ezetimibe .
  The aim of this study was to evaluate the efficacy of adding ezetimibe to simvastatin , atorvastatin , or rosuvastatin monotherapy versus doubling the dosage or switching to a higher-potency statin in a population of patients with hypocholesterolemia at high risk of cardiovascular disease ( CVD ) and who had been previously treated with a statin .