human
***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: 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 ( 45 
    Output:
    
agent
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
***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: 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 ( 45 
    Output:
    