title: Prevalence of Dyslipidemia and Lipid Goal Attainment in Statin-Treated Subjects From 3 Data Sources: A Retrospective Analysis Enhanced low-density lipoprotein cholesterol reduction and cost-effectiveness by low-dose colestipol plus lovastatin combination therapy. Increasing Doses of Simvastatin Versus Combined Ezetimibe/Simvastatin 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 Intensive lowering of LDL cholesterol with 80 mg versus 20 mg simvastatin daily in 12 064 survivors of myocardial infarction: a double-blind randomised trial Niacin in patients with low HDL cholesterol levels receiving intensive statin therapy. Identical LDL-cholesterol lowering but non-identical effects on NF-κB activity: High dose simvastatin vs combination therapy with ezetimibe. Consistency of effect of ezetimibe/simvastatin compared with intensified lipid-lowering treatment strategies in obese and non-obese diabetic subjects The comparative efficacy of ezetimibe added to atorvastatin 10 mg versus uptitration to atorvastatin 40 mg in subgroups of patients aged 65 to 74 years or greater than or equal to 75 years Comparison of Ezetimibe/Simvastatin 10/20 mg Versus Atorvastatin 20 mg in Achieving a Target Low Density Lipoprotein-Cholesterol Goal for Patients With Very High Risk Comparison of anti-inflammatory effects and high-density lipoprotein cholesterol levels between therapy with quadruple-dose rosuvastatin and rosuvastatin combined with ezetimibe Effects of combination lipid therapy in type 2 diabetes mellitus. Comparative effects on lipid levels of combination therapy with a statin and extended-release niacin or ezetimibe versus a statin alone (the COMPELL study). 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). Lipoprotein and apolipoprotein ratios in the VYTAL trial of ezetimibe/simvastatin compared with atorvastatin in type 2 diabetes. Treatment with ezetimibe plus low-dose atorvastatin compared with higher-dose atorvastatin alone: is sufficient cholesterol-lowering enough to inhibit platelets? Efficacy and safety of combination simvastatin and colesevelam in patients with primary hypercholesterolemia. Efficacy and safety of ezetimibe added to atorvastatin versus atorvastatin uptitration or switching to rosuvastatin in patients with primary hypercholesterolemia. A dose‐ranging study of a new, once‐daily, dual‐component drug product containing niacin extended‐release and lovastatin Benefit and tolerability of the coadministration of ezetimibe and atorvastatin in acute coronary syndrome patients. Ezetimibe/simvastatin 10/20 mg versus simvastatin 40 mg in coronary heart disease patients. Flow-mediated dilation in patients with coronary artery disease is enhanced by high dose atorvastatin compared to combined low dose atorvastatin and ezetimibe: results of the CEZAR study. Efficacy of extended-release niacin with lovastatin for hypercholesterolemia: assessing all reasonable doses with innovative surface graph analysis. Effects of Ezetimibe/Simvastatin 10/20 mg vs. Atorvastatin 20 mg on Apolipoprotein B/Apolipoprotein A1 in Korean Patients with Type 2 Diabetes Mellitus: Results of a Randomized Controlled Trial Beneficial effects of the addition of fenofibrate to statin therapy in patients with acute coronary syndrome after percutaneous coronary interventions. Safety and efficacy of ezetimibe/simvastatin combination versus atorvastatin alone in adults ≥65 years of age with hypercholesterolemia and with or at moderately high/high risk for coronary heart disease (the VYTELD study). Atorvastatin versus Four Statin–Fibrate Combinations in Patients with Familial Combined Hyperlipidaemia Ezetimibe/simvastatin vs atorvastatin in patients with type 2 diabetes mellitus and hypercholesterolemia: the VYTAL study. Efficacy of ezetimibe/simvastatin 10/20 and 10/40 mg compared with atorvastatin 20 mg in patients with type 2 diabetes mellitus * Fixed-dose combination fenofibrate/pravastatin 160/40 mg versus simvastatin 20 mg monotherapy in adults with type 2 diabetes and mixed hyperlipidemia uncontrolled with simvastatin 20 mg: a double-blind, randomized comparative study. Efficacy and safety of ezetimibe co-administered with simvastatin in thiazolidinedione-treated type 2 diabetic patients. The Lipid Research Clinics Coronary Primary Prevention Trial results. I. Reduction in incidence of coronary heart disease. 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. Intensive lowering of LDL cholesterol with 80 mg versus 20 mg simvastatin daily in 12,064 survivors of myocardial infarction: a double-blind randomised trial. Pleiotropic effects of ezetimibe/simvastatin vs. high dose simvastatin. Pleiotropic Effects With Equivalent Low-density Lipoprotein Cholesterol Reduction: Comparative Study Between Simvastatin and Simvastatin/Ezetimibe Coadministration
abstract: Background Evidence -based r and omized clinical trials have shown significant benefit of statin treatment with regard to cardiovascular disease . In anticipation of the National Cholesterol Education Program Adult Treatment Panel IV guidelines , we wanted to assess the current state of lipid goal attainment in the high-risk secondary prevention population in the United States . The objectives of the study were to estimate the proportion of high-risk patients treated with statin monotherapy  who achieved Adult Treatment Panel III – recommended low-density lipoprotein cholesterol ( LDL-C ) goals ( < 100 mg/dL ; optional < 70 mg/dL ) as well as non – high-density lipoprotein cholesterol goals ( < 130 mg/dL ; optional < 100 mg/dL ) . Methods and Results This is a cross-sectional , retrospective study of 3 data sources : electronic medical records ( 2003–September 2010 ) , administrative cl aims data ( 2003–2010 ) , and National Health and Nutrition Examination Survey data ( 2007–2008 ) . High-risk patients ( ≥18 years of age ) were defined as those with a history of coronary heart disease or coronary heart disease risk equivalent who had the latest complete lipid panel measurement and had been treated with statin monotherapy for > 90 days at the time of the lipid panel . Cardiovascular disease , coronary heart disease , and coronary heart disease risk equivalents were defined on the basis of availability , specific to each data source . Across the 3 data sources , 20 % to 26 % of high-risk patients treated with statin monotherapy for > 90 days had LDL-C < 70 mg/dL , and 67 % to 77 % had LDL-C < 100 mg/dL. The percentages of those attaining both LDL-C goals and non – high-density lipoprotein cholesterol goals were quantitatively smaller ( 13.5 % to 19.0 % and 46 % to 70 % ) . Conclusions Across the 3 data sources , there was consistency in the proportion of high-risk patients treated with statin monotherapy who were at LDL-C goal . A significant number of these statin-treated patients had additional dyslipidemias A total of 96 patients with moderate elevations of low-density lipoprotein ( LDL ) cholesterol were r and omly assigned to 4 different double-blind treatment regimens : placebo ; colestipol 5 g and lovastatin 20 mg/day ( C5 + L20 ) ; colestipol 10 g and lovastatin 20 mg/day ( C10 + L20 ) ; and lovastatin 40 mg/day ( L40 ) . During 12 weeks of therapy , C10 + L20 achieved the greatest reduction in total cholesterol ( -32 % ) and LDL cholesterol ( -48 % ) levels from baseline . This combination also exhibited significantly greater reductions in LDL cholesterol levels than the C5 + L20 and L40 groups ( p < 0.01 ) . The differences in total and LDL cholesterol reduction between the C5 + L20 and L40 groups were not significant . Similar changes and differences between treatments were seen in apolipoprotein B levels . Whereas mean total apolipoprotein A-I levels increased with all treatments ( p < 0.05 ) , lipoprotein particles A-I were significantly increased in the C10 + L20 group ( p < 0.01 ) only . Results demonstrate that the combination of low-dose lovastatin ( 20 mg/day ) with low-dose colestipol ( 5 or 10 g/day ) produces LDL cholesterol reductions equal to or greater than higher doses of lovastatin ( 40 mg/day ) . In addition , low-dose combinations are > 25 % more cost-effective than high-dose monotherapy Background : Patients with coronary artery disease ( CAD ) should be treated with statins to attain very low cholesterol levels , in order to reduce cardiovascular adverse events . More than 70 % of these patients do not reach the appropriate cholesterol goal despite moderate statin doses . However , it is not known whether therapeutic uptitration with different lipid-lowering strategies has a similar “ pleiotropic ” effect on atherosclerotic endothelial dysfunction evaluated by measurement of endothelial progenitor cells ( EPCs ) . Objective : We sought to compare , in patients with stable CAD and with a low-density lipoprotein cholesterol ( LDL-C ) > 70 mg/dL on treatment with simvastatin 20 mg , the effects on EPCs by increasing simvastatin to 80 mg versus adding ezetimibe 10 mg . Methods : Patients ( n = 68 , 63 ± 9 years , 39 % men ) were r and omly allocated to receive ezetimibe 10/simvastatin 20 mg or simvastatin 80 mg for 6 weeks . Circulating EPCs were measured by flow cytometry before and after the treatment . Results : Both strategies presented similar effects on metabolic parameters . The LDLs were equally reduced by ezetimibe 10/simvastatin 20 mg and simvastatin 80 mg ( 28.9 % ± 13 % vs 21.1 % ± 33 % ; P = .46 , respectively ) . The levels of EPCs were unaffected by ezetimibe 10/simvastatin 20 mg ( median [ 25th , 75th ] : pre- vs posttreatment , 7.0 [ 2.3 ; 13.3 ] vs 3.1 [ 0.1 ; 13.2 ] EPCs/104 mononuclear cells ; P = .43 ) or simvastatin 80 mg ( pre- vs posttreatment , 6.1 [ 2.9 ; 15.2 ] vs 4.0 [ 1.4 ; 10.7 ] EPCs/104 mononuclear cells ; P = .5 ) , and there were no differences between the groups on treatment effects ( P = .9 ) . Conclusions : Among stable patients with CAD and with an LDL-C > 70 mg/dL on simvastatin 20 mg , increasing simvastatin dose to 80 mg or adding ezetimibe 10 mg promoted similar further cholesterol reduction but did not have incremental effects on circulating EPCs . These data suggest that the effects of simvastatin moderate doses on EPCs are not increased by intensive lipid-lowering strategies ( clinical trials.gov : NCT00474123 ) 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 Summary Background Lowering of LDL cholesterol reduces major vascular events , but whether more intensive therapy safely produces extra benefits is uncertain . We aim ed to establish efficacy and safety of more intensive statin treatment in patients at high cardiovascular risk . Methods We undertook a double-blind r and omised trial in 12 064 men and women aged 18–80 years with a history of myocardial infa rct ion . Participants were either currently on or had clear indication for statin therapy , and had a total cholesterol concentration of at least 3·5 mmol/L if already on a statin or 4·5 mmol/L if not . R and omisation to either 80 mg or 20 mg simvastatin daily was done central ly using a minimisation algorithm . Participants were assessed at 2 , 4 , 8 , and 12 months after r and omisation and then every 6 months until final follow-up . The primary endpoint was major vascular events , defined as coronary death , myocardial infa rct ion , stroke , or arterial revascularisation . Analysis was by intention to treat . This study is registered , number IS RCT N74348595 . Findings 6031 participants were allocated 80 mg simvastatin  daily , and 6033 allocated 20 mg simvastatin daily . During a mean follow-up of 6·7 ( SD 1·5 ) years , allocation to 80 mg simvastatin produced an average 0·35 ( SE 0·01 ) mmol/L greater reduction in LDL cholesterol compared with allocation to 20 mg . Major vascular events occurred in 1477 ( 24·5 % ) participants allocated 80 mg simvastatin versus 1553 ( 25·7 % ) of those allocated 20 mg , corresponding to a 6 % proportional reduction ( risk ratio 0·94 , 95 % CI 0·88–1·01 ; p=0·10 ) . There were no apparent differences in numbers of haemorrhagic strokes ( 24 [ 0·4 % ] vs 25 [ 0·4 % ] ) or deaths attributed to vascular ( 565 [ 9·4 % ] vs 572 [ 9·5 % ] ) or non-vascular ( 399 [ 6·6 % ] vs 398 [ 6·6 % ] ) causes . Compared with two ( 0·03 % ) cases of myopathy in patients taking 20 mg simvastatin daily , there were 53 ( 0·9 % ) cases in the 80 mg group . Interpretation The 6 % ( SE 3·5 % ) reduction in major vascular events with a further 0·35 mmol/L reduction in LDL cholesterol in our trial is consistent with previous trials . Myopathy was increased with 80 mg simvastatin daily , but intensive lowering of LDL cholesterol can be achieved safely with other regimens . Funding Merck ; The Clinical Trial Service Unit also receives funding from the UK Medical Research Council and the British Heart Foundation BACKGROUND In patients with established cardiovascular disease , residual cardiovascular risk persists despite the achievement of target low-density lipoprotein ( LDL ) cholesterol levels with statin therapy . It is unclear whether extended-release niacin added to simvastatin to raise low levels of high-density lipoprotein ( HDL ) cholesterol is superior to simvastatin alone in reducing such residual risk . METHODS We r and omly assigned eligible patients to receive extended-release niacin , 1500 to 2000 mg per day , or matching placebo . All patients received simvastatin , 40 to 80 mg per day , plus ezetimibe , 10 mg per day , if needed , to maintain an LDL cholesterol level of 40 to 80 mg per deciliter ( 1.03 to 2.07 mmol per liter ) . The primary end point was the first event of the composite of death from coronary heart disease , nonfatal myocardial infa rct ion , ischemic stroke , hospitalization for an acute coronary syndrome , or symptom-driven coronary or cerebral revascularization . RESULTS A total of 3414 patients were r and omly assigned to receive niacin ( 1718 ) or placebo ( 1696 ) . The trial was stopped after a mean follow-up period of 3 years owing to a lack of efficacy . At 2 years , niacin therapy had significantly increased the median HDL cholesterol level from 35 mg per deciliter ( 0.91 mmol per liter ) to 42 mg per deciliter ( 1.08 mmol per liter ) , lowered the triglyceride level from 164 mg per deciliter ( 1.85 mmol per liter ) to 122 mg per deciliter ( 1.38 mmol per liter ) , and lowered the LDL cholesterol level from 74 mg per deciliter ( 1.91 mmol per liter ) to 62 mg per deciliter ( 1.60 mmol per liter ) . The primary end point occurred in 282 patients in the niacin group ( 16.4 % ) and in 274 patients in the placebo group ( 16.2 % ) ( hazard ratio , 1.02 ; 95 % confidence interval , 0.87 to 1.21 ; P=0.79 by the log-rank test ) . CONCLUSIONS Among patients with atherosclerotic cardiovascular disease and LDL cholesterol levels of less than 70 mg per deciliter ( 1.81 mmol per liter ) , there was no incremental clinical benefit from the addition of niacin to statin therapy during a 36-month follow-up period , despite significant improvements in HDL cholesterol and triglyceride levels . ( Funded by the National Heart , Lung , and Blood Institute and Abbott Laboratories ; AIM -HIGH Clinical Trials.gov number , NCT00120289 . ) OBJECTIVE Lowering LDL-cholesterol by statins has been proven to be associated with reduction of proinflammatory regulators e.g. activation of the transcription factor NF-κB. To our knowledge , anti-inflammatory potential of newer cholesterol lowering agents such as ezetimibe is less intensively studied . Therefore we analyzed the effects of equipotent LDL-lowering therapy with simvastatin alone compared to a combination with ezetimibe on NF-κB activation in peripheral blood mononuclear cells ( P BMC s ) of patients with type 2 diabetes . METHODS Thirty-one patients with type 2 diabetes were included in a double-blind , r and omized trial receiving either 80 mg simvastatin ( sim80 ; n = 10 ) or a combination of 10 mg simvastatin and 10 mg ezetimibe ( sim10eze10 ; n = 11 ) or placebo ( n = 9 ) for eight weeks . NF-κB binding activity and inflammatory markers ( IL-6 , hsCRP ) were analyzed at baseline and after eight weeks of treatment . NF-κB binding activity was analyzed by electrophoretic mobility shift assay . IL-6 and hsCRP were measured by ELISA . RESULTS After eight weeks of treatment LDL-cholesterol was lowered to the same extent in both treatment groups ( p = 0.40 ) but not in placebo . However , patients  taking sim80  showed a significant reduction of mononuclear NF-κB binding activity compared to baseline ( p = 0.009 ) while no effect was observed in the sim10eze10 group ( p = 0.79 ) . Similar differences in anti-inflammatory effects were also observed when analyzing hsCRP ( sim80 : p = 0.03 ; sim10eze10 : p = 0.40 ) and IL-6 levels  ( sim80 : p = 0.15 ; sim10eze10 : p = 0.95 ) . CONCLUSION High dose simvastatin therapy reduces proinflammatory transcription factor NF-κB binding activity and hsCRP levels , while combination of low dose simvastatin with ezetimibe result ing in a similar LDL-reduction does not affect these inflammatory markers 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 Background Coronary heart disease ( CHD ) risk increases with age ; yet lipid-lowering therapies are significantly under-utilized in patients > 65 years . The objective was to evaluate the safety and efficacy of lipid-lowering therapies in older patients treated  with atorvastatin 10 mg + ezetimibe 10 mg ( EZ/Atorva ) vs. increasing the atorvastatin dose to 40 mg . Methods Patients ≥ 65 years with atherosclerotic vascular disease ( LDL-C ≥ 1.81 mmol/L ) or at high risk for coronary heart disease ( LDL-C ≥ 2.59 mmol/L ) were r and omized to EZ/Atorva for 12 wk vs. uptitration to atorvastatin 20 mg for 6 wk followed by atorvastatin 40 mg for 6 wk . The percent change in LDL-C and other lipid parameters and percent patients achieving prespecified LDL-C levels were assessed after 12 wk . Results EZ/Atorva produced greater reductions in most lipid parameters vs. uptitration of atorvastatin in patients ≥ 75 years ( n = 228 ) , generally consistent with patients 65–74 years ( n = 812 ) . More patients achieved LDL-C targets with combination therapy vs. monotherapy in both age groups at 6 wk and in patients ≥ 75 years at 12 wk . At 12 wk , more patients ≥ 75 years achieved LDL-C targets with monotherapy vs. combination therapy . EZ/Atorva produced more favorable improvements in most lipids vs. doubling or quadrupling the atorvastatin dose in patients ≥ 75 years , generally consistent with the findings in patients 65–74 years . Conclusions Our results extended previous findings demonstrating that ezetimibe added to a statin provided a generally well-tolerated therapeutic option for improving the lipid profile in patients 65 to 74 years and ≥ 75 years of age Background and Objectives Although recent lipid-lowering therapies are effective in reducing low density lipoprotein-cholesterol ( LDL-C ) levels , many patients treated with lipid-lowering agents do not achieve target LDL-C levels , especially in very high risk patients . The aim of this study is to compare the effect of ezetimibe/simvastatin 10/20 mg and atorvastatin 20 mg on achieving a target LDL-C goal in very high risk patients . Subjects and Methods A total of 74 patients with very high risk were enrolled in the study . Very high risk patients were defined as patients that displayed established cardiovascular disease with multiple major risk factors , poorly controlled risk factors , multiple risk factors of the metabolic syndrome and acute coronary syndromes . Patients were r and omized into two groups : ezetimibe/simvastatin 10/20 mg ( n=36 ) and atorvastatin 20 mg ( n=38 ) . Follow-up lipid profile was obtained 6 weeks later . A target goal of LDL-C was defined as less than 70 mg/dL at follow-up . Results Baseline clinical and laboratory data were similar between the two groups . Achieving a target LDL-C goal was observed in 41.7 % of Group 1 and 44.7 % of Group 2 at 6 weeks ( p=0.82 ) . Changes in other lipid profiles were not significantly different but the tolerability of the two groups was similar . Conclusion Ezetimibe/simvastatin 10/20 mg and atorvastatin 20 mg showed similar effects in achieving target LDL-C levels in patients with very high risk 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 BACKGROUND We investigated whether combination therapy with a statin plus a fibrate , as compared with statin monotherapy , would reduce the risk of cardiovascular disease in patients with type 2 diabetes mellitus who were at high risk for cardiovascular disease . METHODS We r and omly assigned 5518 patients with type 2 diabetes who were being treated with open-label simvastatin to receive either masked fenofibrate or placebo .  The primary outcome was the first occurrence of nonfatal myocardial infa rct ion , nonfatal stroke , or death from cardiovascular causes . The mean follow-up was 4.7 years . RESULTS The annual rate of the primary outcome was 2.2 % in the fenofibrate group and 2.4 % in the placebo group ( hazard ratio in the fenofibrate group , 0.92 ; 95 % confidence interval [ CI ] , 0.79 to 1.08 ; P=0.32 ) . There were also no significant differences between the two study groups with respect to any secondary outcome . Annual rates of death were 1.5 % in the fenofibrate group and 1.6 % in the placebo group ( hazard ratio , 0.91 ; 95 % CI , 0.75 to 1.10 ; P=0.33 ) . Prespecified subgroup analyses suggested heterogeneity in treatment effect according to sex , with a benefit for men and possible harm for women ( P=0.01 for interaction ) , and a possible interaction according to lipid subgroup , with a possible benefit for patients with both a high baseline triglyceride level and a low baseline level of high-density lipoprotein cholesterol ( P=0.057 for interaction ) . CONCLUSIONS The combination of fenofibrate and simvastatin did not reduce the rate of fatal cardiovascular events , nonfatal myocardial infa rct ion , or nonfatal stroke , as compared with simvastatin alone . These results do not support the routine use of combination therapy with fenofibrate and simvastatin to reduce cardiovascular risk in the majority of high-risk patients with type 2 diabetes . ( Clinical Trials.gov number , NCT00000620 . International guidelines recommend lower target cholesterol levels and treatment of low high-density lipoprotein cholesterol ( HDL-C ) and elevated triglycerides for patients at moderately high to high coronary heart disease ( CHD ) risk . Combination therapy is often required to achieve multiple lipid treatment goals , and > or = 50 % reduction in low-density lipoprotein cholesterol ( LDL-C ) is needed in some patients to achieve aggressive LDL-C targets . In this context , we evaluated comparative effects on lipid levels of combination therapy at low to moderate doses with a statin plus extended-release niacin ( niacin ER ) , a statin plus ezetimibe , and a highly potent statin alone . This was an open-label , multicenter , 12-week study in 292 patients ( 50 % women ) who qualified for drug therapy based on number of CHD risk factors . Patients were r and omized to four parallel arms , titrated from low to moderate or high doses : atorvastatin/niacin ER , rosuvastatin/niacin ER , simvastatin/ezetimibe , or rosuvastatin alone . Baseline mean values were , for LDL-C 197 mg/dL ( 5.1 mmol/L ) , HDL-C 49 mg/dL ( 1.3 mmol/L ) , triglycerides 168 mg/dL ( 1.9 mmol/L ) . There were no significant differences among treatment groups in the change from baseline in LDL-C at pre-specified timepoints during treatment . All groups lowered LDL-C by approximately 50 % or more ( range -49 to -57 % ) , achieving mean levels of 82 - 98 mg/dL ( 2.1 - 2.5 mmol/L ) . Changes in non-HDL-C ( range -46 to -55 % ) mirrored those for LDL-C and did not differ among treatment groups . Statin/niacin ER combination regimens also increased HDL-C and large HDL ( HDL2 ) and lowered triglycerides and lipoprotein ( a ) significantly more than other regimens . No drug-related myopathy or hepatotoxicity was observed . In this study , low to moderate dose combination therapy with a statin and niacin ER provided broad control of lipids and lipoproteins independently associated with CHD 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 BACKGROUND Type 2 diabetes mellitus ( T2DM ) is associated with a high risk for coronary heart disease ( CHD ) . A variety of lipoprotein and apolipoprotein ( Apo ) ratios have been proposed that may reflect the balance of cholesterol delivery and removal at the arterial wall and provide an assessment of CHD risk that is supplemental to low-density lipoprotein cholesterol ( LDL-C ) , the primary guide for cholesterol-lowering therapy in patients at risk . OBJECTIVE To examine changes in lipoprotein and apolipoprotein ratios in the VYTAL trial of hypercholesterolemic patients with T2DM . METHODS Changes in the ratios LDL-C/high-density lipoprotein cholesterol ( HDL-C ) , total cholesterol (TC)/HDL-C , non-HDL-C/HDL-C , and ApoB/ApoA-I were assessed in this r and omized , double-blind , parallel-group study that enrolled T2DM patients with LDL-C ≥100 mg/dL for 6-week treatments with either the usual daily starting doses of atorvastatin ( ATORVA ) 10 or 20 mg or ezetimibe/simvastatin ( EZE/SIMVA ) 10/20 mg , or the next highest doses ( ATORVA 40 mg , EZE/SIMVA 10/40 mg ) . Changes in lipoprotein and apolipoprotein ratios , prespecified exploratory endpoints , were analyzed using analysis of variance . RESULTS Efficacy results were based on 1198 patients with sufficient data among 1229 r and omized patients . Baseline lipoproteins , apolipoproteins , and ratios were comparable among treatment groups . EZE/SIMVA produced significantly greater reductions compared with ATORVA  in each lipoprotein or apolipoprotein ratio at each dose comparison ( P < 0.001 ) . For example , reductions from baseline in TC/HDL-C  were ATORVA 10 mg , -30.2 % ; ATORVA 20 mg -34.9 % ; EZE/SIMVA 10/20 mg , -41.6 % ; ATORVA 40 mg , -37.9 % ; and EZE/SIMVA 10/40 mg , -43.5 % . Tolerability of the two treatments was similar . CONCLUSION For the doses assessed , EZE/SIMVA was more effective compared with ATORVA  in lowering the lipoprotein and apolipoprotein ratios that might be considered secondary measures of CHD risk 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 PURPOSE To examine the efficacy and safety of colesevelam hydrochloride , a novel , nonsystemic , lipid-lowering agent , when coadministered with starting doses of simvastatin in a multicenter , r and omized , double-blind , placebo-controlled trial . PATIENTS AND METHODS Subjects with hypercholesterolemia ( plasma low density lipoprotein [ LDL ] cholesterol level > 160 mg/dL and triglyceride level < or = 300 mg/dL ) were r and omly assigned to receive daily doses of placebo ( n = 33 ) , colesevelam 3.8 g ( recommended dose , n = 37 ) , simvastatin 10 mg ( n = 35 ) , colesevelam 3.8 g with simvastatin 10 mg ( n = 34 ) , colesevelam 2.3 g ( low dose , n = 36 ) , simvastatin 20 mg ( n = 39 ) , or colesevelam 2.3 g with simvastatin 20 mg ( n = 37 ) , for 6 weeks . RESULTS Mean LDL cholesterol levels decreased relative to baseline in the placebo group ( P < 0.05 ) and in all active treatment groups ( P < 0.0001 ) . For groups treated with combination therapy , the mean reduction in LDL cholesterol level was 42 % ( -80 mg/dL ; P < 0.0001 compared with baseline ) , which exceeded the reductions for simvastatin 10 mg ( -26 % , -48 mg/dL ) or 20 mg ( -34 % , -61 mg/dL ) alone , or for colesevelam 2.3 g ( -8 % , -17 mg/dL ) or 3.8 g ( -16 % , -31 mg/dL ) alone ( P < 0.001 ) . The effects of combination therapy on serum HDL cholesterol and triglyceride levels were similar to those for simvastatin alone . Side effects were similar among treatment groups , and there were no clinical ly important changes in laboratory parameters . CONCLUSION Coadministration of colesevelam and simvastatin was effective and well tolerated , providing additive reductions in LDL cholesterol levels compared with either agent alone 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 Background : Combination therapy for dyslipidemia holds promise as effective treatment for patients with multiple lipid disorders , especially those at high risk 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 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 ) BACKGROUND Effects independent from cholesterol reduction on vascular function are considered to importantly contribute to the beneficial effects of statin therapy in cardiovascular disease . We aim ed to evaluate the effect of high versus low dose atorvastatin on endothelial dysfunction in patients with coronary artery disease ( CAD ) in a setting of comparable cholesterol reduction . METHODS AND RESULTS Fifty-eight patients with CAD were r and omly assigned to double-blind treatment for 8 weeks with atorvastatin 80 mg per day ( A80 ) or atorvastatin 10mg+ezetimibe 10 mg per day ( A10E10 ) , respectively . Flow-mediated vasodilation ( FMD ) of the brachial artery , nitroglycerin-mediated endothelium-independent vasodilation ( NMD ) , lipid , C-reactive protein ( CRP ) plasma concentrations and urinary 8-iso-prostagl and in F2alpha excretion were measured before and after treatment . Total cholesterol , triglycerides and LDL-cholesterol levels were significantly reduced with no difference between A80 and A10E10 . A80 caused significantly stronger improvement of FMD compared to A10E10 ( absolute change FMD : A80 + 2.7+/-3.0 % ( post vs. pre p<0.001 ) , A10E10 + 0.6+/-2.9 % ( post vs. pre p=0.25 ) , A80 vs. A10E10 p=0.018 ) . NMD was improved by A80 but not by A10E10 ( absolute change NMD : A80 + 2.7+/-4.6 % , A10E10 + 0.7+/-3.5 % , p=0.12 ) . Both treatment groups caused a comparable reduction of CRP and did not effect urinary 8-iso-prostagl and in F2alpha excretion . There was no correlation between FMD or NMD change and LDL-cholesterol change in either treatment group . CONCLUSIONS The present findings clearly suggest that in the presence of comparable LDL-lowering effects of both treatment forms , LDL-cholesterol independent effects of high dose atorvastatin therapy account for the improvement of endothelium-dependent vasodilation in patients with stable CAD BACKGROUND Combination therapy to improve the total lipid profile may achieve greater coronary risk reductions than lowering low-density lipoprotein cholesterol ( LDL-C ) alone . A new extended-release niacin ( niacin ER)/lovastatin tablet substantially lowers LDL-C , triglyceride , and lipoprotein(a ) levels and raises high-density lipoprotein cholesterol ( HDL-C ) level . We evaluated these serum lipid responses to niacin ER/lovastatin at all clinical ly reasonable doses . METHODS Men ( n = 85 ) and women ( n = 79 ) with type IIa or IIb primary hyperlipidemia after diet were r and omized among 5 parallel treatment arms . Each arm had 5 sequential 4-week treatment periods : niacin ER ( starting at 500 mg/d , increasing in 500-mg increments to 2500 mg/d ) ; lovastatin ( starting at 10 mg , increasing to 20 mg , then 40 mg/d ) ; and 3 combinations arms , each with a constant lovastatin dose and escalating niacin ER doses . RESULTS For primary comparisons , mean LDL-C level reductions from baseline were greater with niacin ER/lovastatin ( 1500/20 mg ) than with lovastatin ( 20 mg ) ( 35 % vs 22 % , P<.001 ) and with niacin ER/lovastatin ( 2000/40 mg ) than with lovastatin ( 40 mg ) ( 46 % vs 24 % , P<.001 ) . Each 500-mg increase in niacin ER , on average , decreased LDL-C levels an additional 4 % and increased HDL-C levels 8 % . The maximum recommended dose ( 2000/40 mg/d ) increased HDL-C levels 29 % and decreased LDL-C levels 46 % , triglyceride levels 38 % , and lipoprotein(a ) levels 14 % . All lipid responses were dose dependent and generally additive . Graphs of the dose-response relationships as 3-dimensional surfaces documented the strength and consistency of these responses . CONCLUSIONS Niacin ER/lovastatin combination therapy substantially improves 4 major lipoprotein levels associated with atherosclerotic disease . Dose-response surfaces provide a practical guide for dose selection Background Although the efficacy of ezetimibe/simvastatin and atorvastatin on traditional lipid parameters has been studied extensively , the apolipoprotein B/apolipoprotein A1 ( ApoB/ApoA1 ) ratio , which has a better predictive value for cardiovascular events , has not previously been used as a primary endpoint in these two treatment groups . Objective Our objective was to compare the efficacy and safety of ezetimibe/simvastatin 10/20 mg versus atorvastatin 20 mg once daily in Korean patients with type 2 diabetes mellitus . Study Design This study was an open-label , r and omized , controlled study . Type 2 diabetes patients with high levels of low-density lipoprotein ( LDL ) cholesterol ( > 100 mg/dL ) were r and omized to receive ezetimibe/simvastatin or atorvastatin . Main Outcome MeasureThe primary endpoint was the difference in the percent change of ApoB/ApoA1 at 12 weeks , and secondary endpoints were changes in lipid profiles , glycosylated hemoglobin ( HbA1c ) , homeostatic model assessment ( HOMA ) index , and C-reactive protein . Results In total , 132 patients ( 66 for each group ) were enrolled and r and omized . After 12 weeks of treatment , the ApoB/ApoA1 ratio was significantly reduced in both groups ; however , the difference of changes between the two groups was not statistically significant ( ezetimibe/simvastatin −38.6 ± 18.0 % vs. atorvastatin −34.4 ± 15.5 % ; p = 0.059 ) . There were no significant differences in changes to total cholesterol , LDL cholesterol , high-density lipoprotein cholesterol , triglycerides , ApoB , and ApoB48 between the two groups . However , the increments of ApoA1 were significantly greater in the ezetimibe/simvastatin group than in the atorvastatin group ( 2.8 ± 10.0 vs. −1.8 ± 9.8 % ; p = 0.002 ) . In the per- protocol analysis , improvement in ApoB/ApoA1 was significantly greater in the ezetimibe/simvastatin group ( −42.8 ± 11.8 vs. −36.7 ± 13.2 % ; p = 0.019 ) . The changes in HbA1c , HOMA index , and C-reactive protein were comparable between the two groups . The adverse reaction rate was similar between the two groups ( 24.2 vs. 34.9 % ; p = 0.180 ) . Conclusion Ezetimibe/simvastatin 10/20 mg is comparable to atorvastatin 20 mg for the management of dyslipidemia , and may have more favorable effects on apolipoprotein profiles than atorvastatin 20 mg in Korean patients with type 2 diabetes mellitus OBJECTIVE To find out whether the addition of fenofibrate to statin monotherapy produced any synergistic or additive beneficial effects in reducing risk factors , especially plasma fibrinogen , in patients with acute coronary syndrome ( ACS ) requiring percutaneous coronary interventions . METHODS A r and omized , non-blinded , prospect i ve study with parallel group design . One hundred two ACS patients who underwent angioplasty were r and omly assigned to atorvastatin ( 20 mg/day , n=25 ) , simvastatin ( 40 mg/day , n=27 ) , atorvastatin-fenofibrate ( 10 mg/day-200 mg/day ) combination ( n=25 ) or simvastatin-fenofibrate ( 20 mg/day-200 mg/day ) combination ( n=25 ) . The serum lipid profile and plasma fibrinogen were recorded before initiation of therapy and after three months of the respective treatments . RESULTS All patients already had desirable lipid levels as per the National Cholesterol Education Program - Adult Treatment Panel III guidelines . The addition of fenofibrate to statin monotherapy produced further benefits to the reduction in triglyceride and very low-density lipoprotein levels , and caused an increase in high-density lipoprotein levels . All the treatment groups showed a significant decrease in the plasma fibrinogen levels . Plasma fibrinogen did not correlate with study parameters such as age , body weight , hemo-dynamic characteristics and lipoprotein levels . Statin monotherapy as well as its combination with fenofibrate produced a significant decrease in the fibrinogen levels . CONCLUSIONS The addition of fenofibrate to statins seems to be beneficial in patients with ACS . Statins decreased plasma fibrinogen significantly , contrary to results from various reports , and the addition of fenofibrate further enhanced this reduction of the novel risk factor fibrinogen Higher than 80 % of coronary heart disease-related mortality occurs in patients ≥65 years of age . Guidelines recommend low-density lipoprotein ( LDL ) cholesterol targets for these at-risk patients ; however , few clinical studies have evaluated lipid-lowering strategies specifically in older adults . This multicenter , 12-week , r and omized , double-blind , parallel-group trial evaluated the efficacy and safety of the usual starting dose of ezetimibe/simvastatin ( 10/20 mg ) versus atorvastatin 10 or 20 mg and the next higher dose of ezetimibe/simvastatin ( 10/40 mg ) versus atorvastatin 40 mg in 1,289 hypercholesterolemic patients ≥65 years of age with or without cardiovascular disease . Patients r and omized to ezetimibe/simvastatin had greater percent decreases in LDL cholesterol ( -54.2 % for 10/20 mg vs -39.5 % and -46.6 % for atorvastatin 10 and 20 mg , respectively ; -59.1 % for 10/40 mg vs -50.8 % for atorvastatin 40 mg ; p < 0.001 for all comparisons ) and the number attaining LDL cholesterol < 70 mg/dl ( 51.3 % for 10/20 mg , 68.2 % for 10/40 mg ) and < 100 mg/dl ( 83.6 % for 10/20 mg ; 90.3 % for 10/40 mg ) was significantly larger compared to those receiving atorvastatin for all prespecified dose comparisons ( p < 0.05 to < 0.001 ) . A significantly larger percentage of high-risk patients achieved LDL cholesterol < 70 mg/dl on ezetimibe/simvastatin 10/20 mg ( 54.3 % ) versus atorvastatin 10 mg ( 10.9 % , p < 0.001 ) or 20 mg ( 28.9 % , p < 0.001 ) and ezetimibe/simvastatin 10/40 mg ( 69.2 % ) versus atorvastatin 40 mg ( 38.2 % , p < 0.001 ) , and a significantly larger percentage of intermediate-risk patients achieved LDL cholesterol < 100 mg/dl on ezetimibe/simvastatin 10/20 mg ( 82.1 % ) versus atorvastatin 10 mg ( 59.3 % , p < 0.05 ) . Improvements in non-high-density lipoprotein cholesterol , total cholesterol , apolipoprotein B , and lipoprotein ratios were significantly greater with ezetimibe/simvastatin than atorvastatin for all comparisons ( p < 0.01 to < 0.001 ) . High-density lipoprotein cholesterol and triglyceride results were variable . All treatments were generally well tolerated . In conclusion , ezetimibe/simvastatin provided significantly greater improvements in key lipid parameters and higher attainment of LDL cholesterol targets than atorvastatin , with comparable tolerability Background Statin – fibrate combinations are very effective in the treatment of familial combined hyperlipidaemia ( FCHL ) . Nonetheless , they have not been extensively used because of the fear of side effects . Thus , a therapeutic alternative is required for this lipid disorder . Objective To compare the long-term ( one-year ) efficacy of atorvastatin monotherapy with those of four statin – fibrate combinations in 675 FCHL patients . Methods Patients were r and omly assigned to atorvastatin monotherapy ( A 20 mg/day ) n=134 , or pravastatin ( P 20 mg/day)+gemfibrozil ( G 1200 mg/day ) n=135 , simvastatin ( S 20 mg/day)+G ( 1200 mg/day ) n=137 , P ( 20 mg/day)+ciciprofibrate ( C 100 mg/day ) n=135 , and S ( 20 mg/day)+C ( 100 mg/day ) n=134 . Results Twelve patients on statin – fibrate combinations were withdrawn from the study because of side effects : Three because of CK elevation , two because of myalgia and seven due to increase in serum transaminase levels . One patient on A was withdrawn because of persistent epigastric discomfort .  Atorvastatin  reduced low density lipoprotein cholesterol and apoprotein B more than all four combinations ( −45 % vs. maximum −40 % of S+C , and −39 % vs. maximum −32 % of the same combination , respectively , P < 0.001 for both ) , but had a lesser effect on triglycerides ( −38 % vs. maximum −53 % of S+C , P=0.0002 ) and high density lipoprotein cholesterol ( 6 % vs. maximum 21 % of S+G , P=0.0003 ) . The effect of A on plasma fibrinogen was analogous to that of G combinations ( −8 % vs. −9 % of P+G and −11 % of S+G , P = NS vs. baseline and among each other ) and inferior to that of the ciprofibrate combinations ( −8 % vs. −24 % of P+C , P=0.0002 and −26 % S+C , P=0.0001 ) . A had a lower treatment cost and better patient compliance , P=0.04 vs. C combinations and P=0.02 vs. G combinations . Conclusions The data suggest that statin – fibrate combinations have a beneficial effect on all lipid parameters . Atorvastatin monotherapy has a better effect on LDL-C and apoprotein B than statin – fibrate combinations , but a lesser effect on HDL-C , TG and in the case of ciprofibrate combinations , fibrinogen . The clinical significance of these findings should be tested in a large , long-term survival study OBJECTIVE To compare the efficacy and safety of the recommended usual starting and next highest doses of ezetimibe/ simvastatin and atorvastatin in patients with type 2 diabetes mellitus and hypercholesterolemia . PATIENTS AND METHODS This double-blind , multicenter study ( June 22 to December 7 , 2005 ) consisted of adult patients r and omized to the recommended usual starting ( ezetimibe/simvastatin , 10/20 mg/d , vs atorvastatin , 10 or 20 mg/d ) or next highest ( ezetimibe/simvastatin , 10/40 mg/d , vs atorvastatin , 40 mg/d ) doses . Efficacy end points included percent changes from baseline in low-density lipoprotein cholesterol ( LDL-C ) levels ( primary ) and proportion of patients attaining LDL-C levels less than 70 mg/dL ( secondary ) . RESULTS A total of 1229 patients participated in the study . Significantly greater mean reductions were found in LDL-C levels with ezetimibe/simvastatin , 10/20 mg/d ( -53.6 % ; 95 % confidence interval [ CI ] , -55.4 % to -51.8 % ) , than with atorvastatin , 10 mg/d ( -38.3 % ; 95 % CI , -40.1 % to -36.5 % ; P < .001 ) or 20 mg/d ( -44.6 % ; 95 % CI , -46.4 % to -42.8 % ; P < .001 ) , and with ezetimibe/simvastatin , 10/40 mg/d ( -57.6 % ; 95 % CI , -59.4 % to -55.8 % ) , vs atorvastatin , 40 mg/d ( -50.9 % ; 95 % CI , -52.7 % to -49.1 % ; P < .001 ) . Ezetimibe/simvastatin was also superior to atorvastatin in attainment of LDL-C levels less than 70 mg/dL ( P < .001 for all dose comparisons ) . Significantly better improvements with ezetimibe/simvastatin than with atorvastatin ( P < or = .001 ) were observed for total cholesterol , high-density lipoprotein cholesterol , and non-high-density lipoprotein cholesterol .  Ezetimibe/ simvastatin , 10/20 mg/d , reduced high-sensitivity C-reactive protein and triglyceride levels significantly more than atorvastatin , 10 mg/d ( P = .02 ) , with comparable reductions at other doses . Incidences of clinical adverse events , including serious drug-related and prespecified gastrointestinal- , gallbladder- , and hepatitis-related allergic reactions or rash events , and laboratory adverse events , including repeated elevation of hepatic transaminases or creatine kinase levels , were similar for both treatments . CONCLUSION Ezetimibe/simvastatin provided additional lipid-modifying benefits over atorvastatin monotherapy at the recommended usual starting and next highest doses in patients with type 2 diabetes . Both treatments were generally well tolerated 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 ) BACKGROUND Patients with type 2 diabetes mellitus and mixed hyperlipidemia have an increased cardiovascular risk and may not achieve recommended LDL-C and non-HDL-C goals on statin monotherapy . This study was design ed to obtain regulatory approval of a fenofibrate/pravastatin 160/40 mg fixed-dose combination ( FDC ) capsule . OBJECTIVE The aim of this study was to compare the efficacy and tolerability of this FDC and simvastatin 20 mg in patients with type 2 diabetes . METHODS This multicenter , r and omized , double-blind , parallel-arm study was conducted in patients with type 2 diabetes and mixed hyperlipidemia , without cardiovascular disease , and who were not at lipid goals with simvastatin 20 mg monotherapy . After a 6-week run-in period during which patients received simvastatin 20 mg , those with non-HDL-C concentrations ≥130 mg/dL or LDL-C concentrations ≥100 mg/dL and triglyceride concentrations 150 to 600 mg/dL were enrolled . Eligible patients were r and omly assigned to receive 12-week treatment with fenofibrate/pravastatin 160/40 mg FDC or simvastatin 20 mg once daily , followed by a 12-week open-label tolerability- assessment period during which all patients received the FDC . The primary efficacy outcome was the mean percentage change in non-HDL-C after 12 weeks . Secondary efficacy outcomes included changes in other lipid and lipoprotein parameters , fibrinogen , and high-sensitivity C-reactive protein . Tolerability was assessed based on the prevalence of adverse events and abnormal laboratory data in each treatment group . RESULTS A total of 291 patients were r and omized to receive fenofibrate/pravastatin ( n= 145 ) or simvastatin ( n = 146 ) . The mean ( SD ) age of the participants was 56.6 ( 8.9 ) years , 48.1 % were men , and the body mass index was 31.3 ( 4.6 ) kg/m(2 ) . The FDC was associated with a significantly greater reduction in non-HDL-C ( primary end point ) compared with simvastatin monotherapy ( -12.9 % [ 1.8 ] vs -6.8 % [ 1.8 ] ; P = 0.008 ) . Triglyceride ( -28.6 % [ 3.7 ] vs + 5.0 % [ 3.6 ] ; P < 0.001 ) , fibrinogen ( -11.5 % [ 1.6 ] vs + 0.3 % [ 1.6 ] ; P < 0.001 ) , and HDL-C ( + 6.3 % [ 1.3 ] vs + 1.8 % [ 1.3 ] ; P = 0.008 ) concentrations also were significantly improved with the FDC compared with simvastatin monotherapy . The proportions of patients who achieved the LDL-C target ( < 100 mg/dL ) were not significantly different between the 2 groups . The proportion of patients who achieved the combined end point of non-HDL-C < 130 mg/dL and LDL-C < 100 mg/dL was significantly greater with fenofibrate/pravastatin compared with simvastatin monotherapy ( 41 [ 28.5 % ] vs 26 [ 17.9 % ] ; P < 0.05 ) . The prevalences of patients who experienced ≥1 adverse event were not statistically different between the fenofibrate/pravastatin and simvastatin groups ( 17.2 % vs 15.1 % ) . However , compared with simvastatin monotherapy , the combination treatment was associated with significantly greater increases in alanine aminotransferase ( + 9.6 % vs + 1.5 % ; P = 0.03 between groups ) , creatinine ( + 13.7 % vs + 6.8 % ; P = 0.002 between groups ) , and homocysteine ( + 36.5 % vs + 1.6 % ; P < 0.001 between groups ) concentrations . CONCLUSIONS In this selected population of adults with type 2 diabetes , the fenofibrate/pravastatin 160/40 mg FDC was associated with significantly greater changes from baseline in non-HDL-C , triglyceride , and HDL-C concentrations  compared with simvastatin 20 mg . Both treatments were well tolerated AIM In patients with type 2 diabetes mellitus ( T2DM ) , combination therapy is usually required to optimize glucose metabolism as well as to help patients achieve aggressive targets for low-density lipoprotein cholesterol ( LDL-C ) and other lipid parameters associated with cardiovascular risk . The thiazolidinediones ( TZDs ) are increasingly being used for both their blood glucose-lowering properties and their modest beneficial effects on triglycerides ( TG ) and high-density lipoprotein cholesterol ( HDL-C ) .  Ezetimibe , an intestinal cholesterol absorption inhibitor , has a mechanism of action that differs from that of statins , which inhibit hepatic cholesterol synthesis . We compared the lipid-modifying efficacy and safety of adding ezetimibe to simvastatin , vs. doubling the dose of simvastatin , in TZD-treated T2DM patients . METHODS This was a r and omized , double-blind , parallel group , multicentre study in T2DM patients , 30 - 75 years of age , who had been on a stable dose of a TZD for at least 3 months and had LDL-C > 2.6 mmol/l ( 100 mg/dl ) prior to study entry . Other antidiabetic medications were also allowed . Following 6 weeks of open-label simvastatin 20 mg/day , patients were r and omized to the addition of either blinded ezetimibe 10 mg/day ( n = 104 ) or an additional blinded simvastatin 20 mg/day ( total simvastatin 40 mg/day ; n = 110 ) for 24 weeks . Patients were stratified according to TZD type and dose ( pioglitazone 15 - 30 vs. 45 mg/day ; rosiglitazone 2 - 4 vs. 8 mg/day ) . RESULTS LDL-C was reduced more ( p < 0.001 ) by adding ezetimibe 10 mg to simvastatin 20 mg ( -20.8 % ) than by doubling the dose of simvastatin to 40 mg ( -0.3 % ) . Ezetimibe plus simvastatin 20 mg also produced significant incremental reductions in non-HDL-C ( p < 0.001 ) , very low-density lipoprotein cholesterol ( p < 0.05 ) and apolipoprotein B ( p < 0.001 ) relative to simvastatin 40 mg . There were no differences between the groups with respect to changes in TG and HDL-C levels , and both treatments were well tolerated . CONCLUSIONS Co-administration of ezetimibe with simvastatin , a dual inhibition treatment strategy targeting both cholesterol synthesis and absorption , is well tolerated and provides greater LDL-C-lowering efficacy than increasing the dose of simvastatin in T2DM patients taking TZDs The Lipid Research Clinics Coronary Primary Prevention Trial ( LRC-CPPT ) , a multicenter , r and omized , double-blind study , tested the efficacy of cholesterol lowering in reducing risk of coronary heart disease ( CHD ) in 3,806 asymptomatic middle-aged men with primary hypercholesterolemia ( type II hyperlipoproteinemia ) . The treatment group received the bile acid sequestrant cholestyramine resin and the control group received a placebo for an average of 7.4 years . Both groups followed a moderate cholesterol-lowering diet . The cholestyramine group experienced average plasma total and low-density lipoprotein cholesterol ( LDL-C ) reductions of 13.4 % and 20.3 % , respectively , which were 8.5 % and 12.6 % greater reductions than those obtained in the placebo group . The cholestyramine group experienced a 19 % reduction in risk ( p less than .05 ) of the primary end point -- definite CHD death and /or definite nonfatal myocardial infa rct ion -- reflecting a 24 % reduction in definite CHD death and a 19 % reduction in nonfatal myocardial infa rct ion . The cumulative seven-year incidence of the primary end point was 7 % in the cholestyramine group v 8.6 % in the placebo group . In addition , the incidence rates for new positive exercise tests , angina , and coronary bypass surgery were reduced by 25 % , 20 % , and 21 % , respectively , in the cholestyramine group . The risk of death from all causes was only slightly and not significantly reduced in the cholestyramine group . The magnitude of this decrease ( 7 % ) was less than for CHD end points because of a greater number of violent and accidental deaths in the cholestyramine group . The LRC-CPPT findings show that reducing total cholesterol by lowering LDL-C levels can diminish the incidence of CHD morbidity and mortality in men at high risk for CHD because of raised LDL-C levels . This clinical trial provides strong evidence for a causal role for these lipids in the pathogenesis of CHD 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 Lowering of LDL cholesterol reduces major vascular events , but whether more intensive therapy safely produces extra benefits is uncertain . We aim ed to establish efficacy and safety of more intensive statin treatment in patients at high cardiovascular risk . METHODS We undertook a double-blind r and omised trial in 12,064 men and women aged 18 - 80 years with a history of myocardial infa rct ion . Participants were either currently on or had clear indication for statin therapy , and had a total cholesterol concentration of at least 3·5 mmol/L if already on a statin or 4·5 mmol/L if not . R and omisation to either 80 mg or 20 mg simvastatin daily was done central ly using a minimisation algorithm . Participants were assessed at 2 , 4 , 8 , and 12 months after r and omisation and then every 6 months until final follow-up . The primary endpoint was major vascular events , defined as coronary death , myocardial infa rct ion , stroke , or arterial revascularisation . Analysis was by intention to treat . This study is registered , number IS RCT N74348595 . FINDINGS 6031 participants were allocated 80 mg simvastatin  daily , and 6033 allocated 20 mg simvastatin daily . During a mean follow-up of 6·7 ( SD 1·5 ) years , allocation to 80 mg simvastatin produced an average 0·35 ( SE 0·01 ) mmol/L greater reduction in LDL cholesterol compared with allocation to 20 mg . Major vascular events occurred in 1477 ( 24·5 % ) participants allocated 80 mg simvastatin versus 1553 ( 25·7 % ) of those allocated 20 mg , corresponding to a 6 % proportional reduction ( risk ratio 0·94 , 95 % CI 0·88 - 1·01 ; p=0·10 ) . There were no apparent differences in numbers of haemorrhagic strokes ( 24 [ 0·4 % ] vs 25 [ 0·4 % ] ) or deaths attributed to vascular ( 565 [ 9·4 % ] vs 572 [ 9·5 % ] ) or non-vascular ( 399 [ 6·6 % ] vs 398 [ 6·6 % ] ) causes . Compared with two ( 0·03 % ) cases of myopathy in patients taking 20 mg simvastatin daily , there were 53 ( 0·9 % ) cases in the 80 mg group . INTERPRETATION The 6 % ( SE 3·5 % ) reduction in major vascular events with a further 0·35 mmol/L reduction in LDL cholesterol in our trial is consistent with previous trials . Myopathy was increased with 80 mg simvastatin daily , but intensive lowering of LDL cholesterol can be achieved safely with other regimens . FUNDING Merck ; The Clinical Trial Service Unit also receives funding from the UK Medical Research Council and the British Heart Foundation 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 Background : Coadministration of any statin with ezetimibe is as effective as using high doses of the same statin in the reduction of low-density lipoprotein cholesterol ( LDL-c ) . There may be other effects called pleiotropics . Objective : To compare the effectiveness of 2 different treatments that obtain equivalent LDL-c reductions ( 80 mg of simvastatin , once a day and coadministration of 10 mg of simvastatin and 10 mg of ezetimibe , once a day ) over endothelial function and inflammation . Methods : Twenty-three r and omized patients with hypercholesterolemia in a 2 × 2 crossover protocol were studied . Endothelial function was analyzed by ultrasound assessment of endothelial dependent flow-mediated vasodilation of the brachial artery , and inflammation was estimated by high-sensitivity C-reactive protein ( hs-CRP ) . Results : LDL-c reduction was similar between the 2 treatments with simvastatin/ezetimibe and with simvastatin ( P < 0.001 ) ; no difference between treatments was found ( P = 0.968 ) . Both treatments improved significantly the endothelial function [ 3.61 % with simvastatin/ezetimibe ( P = 0.003 ) and 5.08 % with simvastatin ( P < 0.001 ) ] ; no difference was found between the 2 treatments ( P = 0.291 ) . hs-CRP had a 23 % reduction with simvastatin/ezetimibe ( P = 0.004 ) and a 30 % reduction with simvastatin alone ( P = 0.01 ) , with no significant difference between the 2 treatments ( P = 0.380 ) . Conclusion : The 2 forms of treatment presented similar pleiotropic effects : improvement in endothelial function and decrease in hs-CRP levels
target: Population Characteristics and Study Quality of Included Trials , by Combination Therapy Agent and Potency Comparison Long-Term Clinical Outcomes We found insufficient evidence to compare long-term clinical outcomes ( mortality , acute coronary events , cerebrovascular events , and revascularization procedures ) for all combination therapy and statin intensity comparisons .
  Figure 1 presents an evidence map of studies that evaluated these
background: Atherosclerotic cardiovascular disease ( ASCVD ) affects more than 15 million Americans ( 1 ) and is the leading cause of death for both men and women in the United States ( 2 ) .
  Trials have demonstrated reductions in low-density lipoprotein ( LDL ) cholesterol levels ( 3 ) and decreased ASCVD risk with 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor ( statin ) monotherapy ( 4 ) .
  Over the past decade , statins have often been used in combination with other lipid-modifying agents .
  Recently , several high-profile r and omized , controlled trials ( RCTs ) have evaluated add-on therapy ( 57 ) , wherein statin monotherapy is compared with the combination of the same statin dose and another lipid-modifying agent .
  Add-on combination therapy can lead to superior lipid outcomes , but studies have not shown decreased rates of cardiovascular death , myocardial infa rct ion , revascularization , or stroke ( 57 ) .
  Therefore , the 2013 American College of Cardiology ( ACC ) and American Heart Association ( AHA ) guidelines recommend moderate- or high-intensity statin monotherapy as the first-line strategy for ASCVD risk reduction among patients with LDL cholesterol levels of 4.91 mmol/L or greater ( 190 mg/dL ) , preexisting ASCVD , diabetes mellitus ( DM ) , or estimated 10-year ASCVD risk of 7.5 % or greater ( 8) .
  Adverse effects are more common with higher-intensity statin regimens ( 9 ) , and musculoskeletal adverse events occur frequently among patients with the C variant in the SLCO1B1 gene ( 10 ) .
  The 2013 ACC/AHA guidelines suggest that clinicians consider moderated combination therapy with a lower-intensity statin and another lipid-modifying medication among high-risk patients ( LDL cholesterol level 4.91 mmol/L [ 190 mg/dL ] , preexisting ASCVD , or DM ) who are intolerant of or unresponsive to statins ( evidence grade E : expert opinion ) ( 8) .
  Yet , it is unclear whether this strategy results in similar ASCVD risk reductions and fewer adverse effects compared with higher-intensity statin monotherapy .
  A 2009 systematic review that examined these questions found insufficient evidence to weigh benefits and risks of moderated combination therapy ( 12 ) .
  We aim ed to compare the effectiveness , safety , and tolerability of moderated combination therapy of statin with another lipid-modifying medication ( bile acid sequestrant , ezetimibe , fibrate , niacin , or -3 fatty acid ) with those of higher-intensity statin monotherapy among high-risk patients .
  We sought to compare the long-term clinical benefits and short-term lipid effects of moderated combination therapy with those of higher-intensity statin monotherapy , as well as to determine whether these regimens differ in rates of adherence and harms .
  Given the recent release of the 2013 ACC/AHA guidelines ( 8) , we narrowed the scope of this manuscript to focus on evidence most relevant to high-risk population s for whom combination therapy might be considered .
  Prior studies have suggested schemes to group statins on the basis of their reported LDL cholesterol reduction ( 17 , 18 ) , which are similar to the strategy used by the ACC/AHA committee ( 8) .