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: 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 dec 
    Output:
    
agent
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
***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: 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 dec 
    Output:
    