***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: OBJECTIVE The purpose of this study was to evaluate the efficacy and safety profile of ezetimibe/simvastatin(EZE/SIMVA ) combination tablet , relative to ezetimibe ( EZE ) and simvastatin ( SIMVA ) monotherapy , in patients with primary hypercholesterolemia . METHODS This was a r and omized , multicenter , double-blind , placebo-controlled , factorial design study After a 6- to 8-week washout period and 4-week , single-blind , placebo run in , hypercholesterolemic patients ( low-density lipoprotein cholesterol [ LDL-C ] , 145 - 250 mg/dL ; triglycerides [ TG ] , < or = 350 mg/dL ) were r and omized equally to 1 of 10 daily treatments for 12 weeks : EZE/SIMVA 10/10 , 10/20 , 10/40 , or 10/80 mg ; SIMVA 10 , 20 , 40 , or 80 mg ; EZE 10 mg ; or placebo . The primary efficacy analysis was mean percent change from baseline in LDL-C to study end point Secondary end points included percent changes in other lipid variables and C-reactive protein [ CRP ] . RESULTS There were 1528 patients r and omized to treatment ( 792 women , 736 men ) ; mean ( SD ) age ranged from 54.9 ( 112 ) years to 56.4 ( 10.6 ) years across pooled treatment groups . The treatment groups were well balanced for baseline demographics . Pooled EZE/SIMVA was associated with greater reductions in LDL-C than pooled SIMVA or EZE alone ( P < 0.001 ) . Depending on dose , EZE/SIMVA was associated with reductions in LDL-C of -44.8 % to -602 % , non-high-density lipoprotein cholesterol of -40.5 % to -55.7 % , and TG of -22.5 % to -30.7 % ; high-density lipoprotein cholesterol increased by 5.5 % to 9.8 % . EZE/SIMVA was associated with greater reductions in CRP and remnant-like particle-cholesterol than SIMVA alone ( P < 0.001 ) . More patients receiving EZE/SIMVA versus SIMVA achieved LDL-C concentrations < 100 mg/dL ( 78.6 % vs 45.9 % ; P < 0.001 ) . EZE/SIMVA was generally well tolerated , with a safety profile similar to SIMVA monotherapy There were no significant differences between EZE/SIMVA and SIMVA in the incidence of consecutive liver transaminase levels > or =3 times the upper limit of normal ( ULN ) ( 1 .5 % for EZE/SIMVA and 1.1 % for SIMVA ; P = NS ) or creature kinase levels > or = 10 times ULN ( 0.0 % for EZE/SIMVA and 02 % for SIMVA ; P = NS ) . CONCLUSION The EZE/SIMVA tablet was a highly effective and well-tolerated LDL-C-lowering therapy in this study of patients with primary hypercholesterolemia Background —Despite the established efficacy of statins , many patients do not achieve recommended LDL cholesterol ( LDL-C ) goals . Contributing factors may be inadequate dosing , increased risk for adverse effects with high-dose monotherapy , and increased potential for intolerance and adverse effects with combinations of available agents . Methods and Results —In a double-blind study , 628 patients with baseline LDL-C 145 to 250 mg/dL and triglycerides ≤350 mg/dL were r and omly assigned to receive 1 of the following for 12 weeks : ezetimibe ( 10 mg/d ) ; atorvastatin ( 10 , 20 , 40 , or 80 mg/d ) ; ezetimibe ( 10 mg ) plus atorvastatin ( 10 , 20 , 40 , or 80 mg/d ) ; or placebo . The primary efficacy end point was percentage reduction in LDL-C for pooled ezetimibe plus atorvastatin versus pooled atorvastatin treatment groups . Ezetimibe plus atorvastatin significantly improved LDL-C , HDL cholesterol ( HDL-C ) , triglycerides , total cholesterol : HDL-C , and high-sensitivity C-reactive protein ( hs-CRP ) compared with atorvastatin alone ( P < 0.01 ) . Coadministration of ezetimibe provided a significant additional 12 % LDL-C reduction , 3 % HDL-C increase , 8 % triglyceride reduction , and 10 % hs-CRP reduction versus atorvastatin alone . Ezetimibe plus atorvastatin  provided LDL-C reductions of 50 % to 60 % , triglyceride reductions of 30 % to 40 % , and HDL-C increases of 5 % to 9 % , depending on atorvastatin dose . LDL-C reductions with ezetimibe plus 10 mg atorvastatin ( 50 % ) and 80 mg atorvastatin alone ( 51 % ) were similar . Conclusions —Ezetimibe plus atorvastatin was well tolerated , with a safety profile similar to atorvastatin alone and to placebo . When coadministered with atorvastatin , ezetimibe provided significant incremental reductions in LDL-C and triglycerides and increases in HDL-C. Coadministration of ezetimibe and atorvastatin offers a well-tolerated and highly efficacious new treatment option for patients with hypercholesterolemia OBJECTIVES The purpose of this study was to assess the efficacy and safety of ezetimibe administered with simvastatin in patients with primary hypercholesterolemia . BACKGROUND Despite the availability of statins , many patients do not achieve lipid targets . Combination therapy with lipid-lowering agents that act via a complementary pathway may allow additional patients to achieve recommended cholesterol goals . METHODS After dietary stabilization , a 2- to 12-week washout period , and a 4-week , single-blind , placebo lead-in period , patients with baseline low-density lipoprotein cholesterol ( LDL-C ) > or = 145 mg/dl to < or = 250 mg/dl and triglycerides ( TG ) < or = 350 mg/dl were r and omized to one of the following 10 groups administered daily for 12 consecutive weeks : ezetimibe 10 mg ; simvastatin 10 , 20 , 40 , or 80 mg ; ezetimibe 10 mg plus simvastatin 10 , 20 , 40 , or 80 mg ; or placebo . The primary efficacy variable was percentage reduction from baseline to end point in direct LDL-C for the pooled ezetimibe plus simvastatin groups versus pooled simvastatin groups . RESULTS Ezetimibe plus simvastatin significantly improved LDL-C ( p < 0.01 ) , high-density lipoprotein cholesterol ( HDL-C ) ( p = 0.03 ) , and TG ( p < 0.01 ) compared with simvastatin alone . Ezetimibe plus simvastatin ( pooled doses ) provided an incremental 13.8 % LDL-C reduction , 2.4 % HDL-C increase , and 7.5 % TG reduction compared with pooled simvastatin alone . Coadministration of ezetimibe and simvastatin provided LDL-C reductions of 44 % to 57 % , TG reductions of 20 % to 28 % , and HDL-C increases of 8 % to 11 % , depending on the simvastatin dose . Ezetimibe 10 mg plus simvastatin 10 mg and simvastatin 80 mg alone each provided a 44 % LDL-C reduction . The coadministration of ezetimibe with simvastatin was well tolerated , with a safety profile similar to those of simvastatin and of placebo . CONCLUSIONS When coadministered with simvastatin , ezetimibe provided significant incremental reductions in LDL-C and TG , as well as increases in HDL-C. Coadministration of ezetimibe with simvastatin was well tolerated and comparable to statin alone The efficacy and safety of ezetimibe , a new cholesterol absorption inhibitor , was evaluated in this r and omized , double-blind , placebo-controlled trial of 892 patients with primary hypercholesterolemia . After > or = 2 weeks on the National Cholesterol Education Program ( NCEP ) Step I or a stricter diet and a 4- to 8-week single-blind placebo lead-in , patients with low-density lipoprotein ( LDL ) cholesterol 130 to 250 mg/dl and triglycerides < or = 350 mg/dl were r and omized 3:1 to receive ezetimibe 10 mg or placebo orally each morning for 12 weeks . The primary efficacy end point was the percent reduction in direct plasma LDL cholesterol from baseline to end point . A total of 434 men and 458 women ( ages 18 to 85 years ) received r and omized treatment ( 666 ezetimibe 10 mg , 226 placebo ) . Demographics and baseline characteristics were similar between treatment groups . Ezetimibe significantly reduced direct LDL cholesterol by a mean of 16.9 % , compared with an increase of 0.4 % with placebo ( p < 0.01 ) . Subgroup analysis indicated that response to ezetimibe was generally consistent across all subgroups , regardless of risk-factor status , gender , age , race , or baseline lipid profile . Ezetimibe effects on LDL cholesterol occurred early ( 2 weeks ) and persisted throughout the 12-week treatment period . Compared with placebo , ezetimibe 10 mg also significantly improved calculated LDL cholesterol , apolipoprotein B , total cholesterol , triglycerides , high-density lipoprotein ( HDL ) cholesterol , and HDL(3 ) cholesterol ( p < 0.01 ) . Ezetimibe was well tolerated . There were no differences in laboratory or clinical safety parameters , or gastrointestinal , liver , or muscle side effects from that of placebo . Ezetimibe 10 mg/day is well tolerated , reduces LDL cholesterol approximately 17 % , and improves other key lipid parameters BACKGROUND With increased efforts to lower serum cholesterol levels , it is important to quantify associations between serum cholesterol level and causes of death other than coronary heart disease , for which an etiologic relationship has been established . METHODS For an average of 12 years , 350,977 men aged 35 to 57 years who had been screened for the Multiple Risk Factor Intervention Trial were followed up following a single st and ardized measurement of serum cholesterol level and other coronary heart disease risk factors ;  21,499 deaths were identified . RESULTS A strong , positive , grade d relationship was evident between serum cholesterol level measured at initial screening and death from coronary heart disease . This relationship persisted over the 12-year follow-up period . No association was noted between serum cholesterol level and stroke . The absence of an association overall was due to different relationships of serum cholesterol level with intracranial hemorrhage and nonhemorrhagic stroke . For the latter , a positive , grade d association with serum cholesterol level was evident . For intracranial hemorrhage , cholesterol levels less than 4.14 mmol/L ( less than 160 mg/dL ) were associated with a twofold increase in risk . A serum cholesterol level less than 4.14 mmol/L ( less than 160 mg/dL ) was also associated with a significantly increased risk of death from cancer of the liver and pancreas ; digestive diseases , particularly hepatic cirrhosis ; suicide ; and alcohol dependence syndrome . In addition , significant inverse grade d associations were found between serum cholesterol level and cancers of the lung , lymphatic , and hematopoietic systems , and chronic obstructive pulmonary disease . No significant associations were found of serum cholesterol level with death from colon cancer , with accidental deaths , or with homicides . Overall , the inverse association between serum cholesterol level and most cancers weakened with increasing follow-up but did not disappear . The association between cholesterol level and death due to cancer of the lung and liver , chronic obstructive pulmonary disease , cirrhosis , and suicide weakened little over follow-up . CONCLUSIONS The association of serum cholesterol with specific causes of death varies in direction , strength , gradation , and persistence . Further research on the determinants of low serum cholesterol level in population s and long-term follow-up of participants in clinical trials are necessary to assess whether inverse associations with noncardiovascular disease causes of death are consequences of noncardiovascular disease , whether serum cholesterol level and noncardiovascular disease are both consequences of other factors , or whether these associations are causal BACKGROUND Hyperlipidemia has been suggested as a risk factor for stenosis of the aortic valve , but lipid-lowering studies have had conflicting results . METHO 
    Output:
    
Ezetimibe monotherapy appeared to be well tolerated with a safety profile similar to placebo .
In a meta- analysis restricted to short-term trials in hypercholesterolaemia , significant potentially favourable changes in lipid and lipoprotein levels relative to baseline occurred with ezetimibe monotherapy .