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 The effects of cholesterol-lowering treatment with statins on mortality and risk of cancer beyond the usual 5 - 6-year trial periods are unknown . We extended post-trial follow-up of participants in the Sc and inavian Simvastatin Survival Study ( 4S ) to investigate cause-specific mortality and incidence of cancer 5 years after closure of the trial . METHODS 4S was a r and omised double-blind trial of simvastatin or placebo in patients with coronary heart disease , serum total cholesterol 5.5 - 8.0 mmol/L , and serum triglycerides 2.5 mmol/L or lower . The double-blind period lasted for a median of 5.4 years ( range for survivors 4.9 - 6.3 ) and ended in 1994 . After the trial , most patients in both groups received open-label lipid-lowering treatment . National registers were used to assess mortality and causes of death and cancer incidence in the original treatment groups for a median total follow-up time of 10.4 years ( range for survivors 9.9 - 11.3 ) . Analysis was by intention to treat . FINDINGS 414 patients originally allocated simvastatin and 468 assigned placebo  died during the 10.4-year follow-up ( relative risk 0.85 [ 95 % CI 0.74 - 0.97 ] , p=0.02 ) , a difference largely attributable to lower coronary mortality in the simvastatin group ( 238 vs 300 deaths ; 0.76 [ 0.64 - 0.90 ] , p=0.0018 ) . 85 cancer deaths arose in the simvastatin group versus 100 in the placebo group ( 0.81 [ 0.60 - 1.08 ] , p=0.14 ) , and 227 incident cancers were reported in the simvastin group versus 248 in the placebo group ( 0.88 [ 0.73 - 1.05 ] , p=0.15 ) . Incidence of any specific type of cancer did not rise in the simvastatin group . INTERPRETATION Simvastatin treatment for 5 years in a placebo-controlled trial , followed by open-label statin therapy , was associated with survival benefit over 10 years of follow-up compared with open-label statin therapy for the past 5 years only . No difference was noted in mortality from and incidence of cancer between the original simvastatin group and placebo group BACKGROUND The PREVEND IT investigated whether treatment targeted at lowering urinary albumin excretion ( UAE ) would reduce adverse cardiovascular events . We obtained extended follow-up data to approximately 10 years to investigate the long-term effects of fosinopril 20 mg and pravastatin 40 mg on cardiovascular outcomes in subjects with UAE > 15 mg per 24 hours . METHODS The original PREVEND IT consisted of 864 participants and 839 survivors after 4 years . For every survivor , the primary end point determined by the combined incidence of cardiovascular mortality and hospitalization for cardiovascular morbidity was registered in several national data bases and electronic hospital systems . RESULTS Mean total follow-up of the extended PREVEND IT was 9.5 years ( range 9.4 - 10.7 years ) . Four years of treatment with fosinopril was not associated with a reduction in the primary end point compared with placebo ( hazard ratio 0.87 , 95 % CI 0.61 - 1.24 [ P = .42 ] ) during long-term follow-up . After 9.5 years , subjects with a baseline UAE in the upper quintile ( > 50 mg/24 hours ) had a total event rate of 29.5 % and were at a higher risk for developing cardiovascular disease compared with less UAE ( hazard ratio 2.03 , 95 % CI 1.38 - 2.97 [ P ≤ .01 ] ) . In addition , 4 years of fosinopril treatment result ed in a risk reduction of 45 % ( 95 % CI 6%-75 % [ P = .04 ] ) in this group compared with placebo . Subjects originally assigned to pravastatin had no overall risk reduction in the primary end point ( P = .99 ) . CONCLUSIONS Elevated UAE is associated with increased cardiovascular mortality and morbidity after 9.5 years of follow-up , with a doubling of the risk if the UAE is > 50 mg per 24 hours . In this group , the benefits of 4-year treatment with fosinopril were sustained during posttrial follow-up for cardiovascular mortality and morbidity . We propose that UAE be used to estimate risk in the general population and that large clinical trials be design ed to confirm the hypothesis that angiotensin-converting enzyme-inhibitor treatment may be beneficial in patients with mildly elevated UAE despite the absence of other comorbidities Background The PROspect i ve Study of Pravastatin in the Elderly at Risk ( PROSPER ) , a placebo-controlled trial of pravastatin , demonstrated a 19 % reduction in coronary outcomes ( p = 0.006 ) after a mean of 3.2 years , with no impact on stroke outcomes or all-cause mortality . However , there was a suggestion of increased cancer risk . Our aim is to determine the long-term benefits and safety of pravastatin treatment in older people using post-trial follow-up of the PROSPER participants . Methods 5,804 ( 2,520 Scottish ) men and women aged 70–82 years with either pre-existing vascular disease or increased risk of such disease because of smoking , hypertension or diabetes , were r and omised to 40 mg pravastatin or matching placebo . Using record linkage to routinely collected health records , all participants ( full cohort ) were linked to death and cancer registries , and the Scottish cohort additionally to hospital admissions , to provide composite fatal/non-fatal cardiovascular outcomes ( total mean follow-up 8.6 years ) . Results Pravastatin treatment for 3.2 years reduced CHD death in the full cohort , hazard ratio ( HR ) 0.80 , 95 % confidence interval ( CI ) 0.68–0.95 , p = 0.0091 and fatal coronary events or coronary hospitalisations in the Scottish cohort ( HR 0.81 , 95 % CI 0.69–0.95 , p = 0.0081 ) over 8.6 years . There was no reduction in stroke or all-cause mortality . Cancer risk was not increased in the full cohort ( HR 1.08 , 95 % CI 0.96–1.21 , p = 0.22 ) . Conclusions Pravastatin treatment of elderly high-risk subjects for 3.2 years provided long-term protection against CHD events and CHD mortality . However , this was not associated with any increase in life expectancy , possibly due to competing mortality with deaths from other causes . There was no evidence of long-term increased risk of cancer . Trial registration IS RCT N40976937 BACKGROUND Post-trial monitoring of patients in the United Kingdom Prospect i ve Diabetes Study ( UKPDS ) examined whether risk reductions for microvascular and macrovascular disease , achieved with the use of improved blood-pressure control during the trial , would be sustained . METHODS Among 5102 UKPDS patients with newly diagnosed type 2 diabetes mellitus , we r and omly assigned , over a 4-year period beginning in 1987 , 1148 patients with hypertension to  tight or less-tight blood-pressure control regimens .  The 884 patients who underwent post-trial monitoring  were asked to attend annual UKPDS clinics for the first 5 years , but no attempt was made to maintain their previously assigned therapies . Annual question naires completed by patients and general practitioners were used to follow patients who were unable to attend the clinic in years 1 through 5 , and question naires were used for all patients in years 6 to 10 . Seven prespecified aggregate clinical end points were examined on an intention-to-treat basis , according to the previous r and omization categories . RESULTS Differences in blood pressure between the two groups during the trial disappeared within 2 years after termination of the trial . Significant relative risk reductions found during the trial for any diabetes-related end point , diabetes-related death , microvascular disease , and stroke in the group receiving tight , as compared with less tight , blood-pressure control were not sustained during the post-trial follow-up . No risk reductions were seen during or after the trial for myocardial infa rct ion or death from any cause , but a risk reduction for peripheral vascular disease associated with tight blood-pressure control became significant ( P=0.02 ) . CONCLUSIONS The benefits of previously improved blood-pressure control were not sustained when between-group differences in blood pressure were lost . Early improvement in blood-pressure control in patients with both type 2 diabetes and hypertension was associated with a reduced risk of complications , but it appears that good blood-pressure control must be continued if the benefits are to be maintained . ( UKPDS 81 ; Current Controlled Trials number , IS RCT N75451837 . BACKGROUND Treatment with angiotensin-converting-enzyme ( ACE ) inhibitors reduces mortality among survivors of acute myocardial infa rct ion , but whether to use ACE inhibitors in all patients or only in selected patients is uncertain . METHODS We screened 6676 consecutive patients with 7001 myocardial infa rct ions confirmed by enzyme studies . A total of 2606 patients had echocardiographic evidence of left ventricular systolic dysfunction ( ejection fraction , < or = 35 percent ) . On days 3 to 7 after infa rct ion , 1749 patients were r and omly assigned to receive oral tr and olapril ( 876 patients ) or placebo ( 873 patients ) . The duration of follow-up was 24 to 50 months . RESULTS During the study period , 304 patients ( 34.7 percent ) in the tr and olapril group died , as compared with 369 ( 42.3 percent ) in the placebo group ( P = 0.001 ) . The relative risk of death in the tr and olapril group , as compared with the placebo group , was 0.78 ( 95 percent confidence interval , 0.67 to 0.91 ) . Tr and olapril also reduced the risk of death from cardiovascular causes ( relative risk , 0.75 ; 95 percent confidence interval , 0.63 to 0.89 ; P = 0.001 ) and sudden death ( relative risk , 0.76 ; 95 percent confidence interval , 0.59 to 0.98 ; P = 0.03 ) . Progression to severe heart failure was less frequent in the tr and olapril group ( relative risk , 0.71 ; 95 percent confidence interval , 0.56 to 0.89 ; P = 0.003 ) . In contrast , the risk of recurrent myocardial infa rct ion ( fatal or nonfatal ) was not significantly reduced ( relative risk , 0.86 ; 95 percent confidence interval , 0.66 to 1.13 ; P = 0.29 ) . CONCLUSIONS Long-term treatment with tr and olapril in patients with reduced left ventricular function soon after myocardial infa rct ion significantly reduced the risk of overall mortality , mortality from cardiovascular causes , sudden death , and the development of severe heart failure . That mortality was reduced in a r and omized study enrolling 25 percent of consecutive patients screened should encourage the selective use of ACE inhibition after myocardial infa rct ion BACKGROUND Although statins reduce coronary and cerebrovascular morbidity and mortality in middle-aged individuals , their efficacy and safety in elderly people is not fully established . Our aim was to test the benefits of pravastatin treatment in an elderly cohort of men and women with , or at high risk of developing , cardiovascular disease and stroke . METHODS We did a r and omised controlled trial in which we assigned 5804 men ( n=2804 ) and women ( n=3000 ) aged 70 - 82 years with a history of , or risk factors for , vascular disease to pravastatin ( 40 mg per day ; n=2891 ) or placebo ( n=2913 ) . Baseline cholesterol concentrations ranged from 4.0 mmol/L to 9.0 mmol/L. Follow-up was 3.2 years on average and our primary endpoint was a composite of coronary death , non-fatal myocardial infa rct ion , and fatal or non-fatal stroke . Analysis was by intention-to-treat . FINDINGS Pravastatin lowered LDL cholesterol concentrations by 34 % and reduced the incidence of the primary endpoint to 408 events compared with 473 on placebo ( hazard ratio 0.85 , 95 % CI 0.74 - 0.97 , p=0.014 ) . Coronary heart disease death and non-fatal myocardial infa rct ion risk was also reduced ( 0.81 , 0.69 - 0.94 , p=0.006 ) . Stroke risk was unaffected ( 1.03 , 0.81 - 1.31 , p=0.8 ) , but the hazard ratio for transient ischaemic attack was 0.75 ( 0.55 - 1.00 , p=0.051 ) . New cancer diagnoses were 
    Output:
    
agent
Results : BP and lipid levels tended to come together soon in the post-trial period .
Conclusion : Benefits of BPL and lipid lowering on all-cause and cardiovascular mortality were persistent , but attenuated , after discontinuation of r and omized treatment , indicating the importance of continuing therapy
***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 The effects of cholesterol-lowering treatment with statins on mortality and risk of cancer beyond the usual 5 - 6-year trial periods are unknown . We extended post-trial follow-up of participants in the Sc and inavian Simvastatin Survival Study ( 4S ) to investigate cause-specific mortality and incidence of cancer 5 years after closure of the trial . METHODS 4S was a r and omised double-blind trial of simvastatin or placebo in patients with coronary heart disease , serum total cholesterol 5.5 - 8.0 mmol/L , and serum triglycerides 2.5 mmol/L or lower . The double-blind period lasted for a median of 5.4 years ( range for survivors 4.9 - 6.3 ) and ended in 1994 . After the trial , most patients in both groups received open-label lipid-lowering treatment . National registers were used to assess mortality and causes of death and cancer incidence in the original treatment groups for a median total follow-up time of 10.4 years ( range for survivors 9.9 - 11.3 ) . Analysis was by intention to treat . FINDINGS 414 patients originally allocated simvastatin and 468 assigned placebo  died during the 10.4-year follow-up ( relative risk 0.85 [ 95 % CI 0.74 - 0.97 ] , p=0.02 ) , a difference largely attributable to lower coronary mortality in the simvastatin group ( 238 vs 300 deaths ; 0.76 [ 0.64 - 0.90 ] , p=0.0018 ) . 85 cancer deaths arose in the simvastatin group versus 100 in the placebo group ( 0.81 [ 0.60 - 1.08 ] , p=0.14 ) , and 227 incident cancers were reported in the simvastin group versus 248 in the placebo group ( 0.88 [ 0.73 - 1.05 ] , p=0.15 ) . Incidence of any specific type of cancer did not rise in the simvastatin group . INTERPRETATION Simvastatin treatment for 5 years in a placebo-controlled trial , followed by open-label statin therapy , was associated with survival benefit over 10 years of follow-up compared with open-label statin therapy for the past 5 years only . No difference was noted in mortality from and incidence of cancer between the original simvastatin group and placebo group BACKGROUND The PREVEND IT investigated whether treatment targeted at lowering urinary albumin excretion ( UAE ) would reduce adverse cardiovascular events . We obtained extended follow-up data to approximately 10 years to investigate the long-term effects of fosinopril 20 mg and pravastatin 40 mg on cardiovascular outcomes in subjects with UAE > 15 mg per 24 hours . METHODS The original PREVEND IT consisted of 864 participants and 839 survivors after 4 years . For every survivor , the primary end point determined by the combined incidence of cardiovascular mortality and hospitalization for cardiovascular morbidity was registered in several national data bases and electronic hospital systems . RESULTS Mean total follow-up of the extended PREVEND IT was 9.5 years ( range 9.4 - 10.7 years ) . Four years of treatment with fosinopril was not associated with a reduction in the primary end point compared with placebo ( hazard ratio 0.87 , 95 % CI 0.61 - 1.24 [ P = .42 ] ) during long-term follow-up . After 9.5 years , subjects with a baseline UAE in the upper quintile ( > 50 mg/24 hours ) had a total event rate of 29.5 % and were at a higher risk for developing cardiovascular disease compared with less UAE ( hazard ratio 2.03 , 95 % CI 1.38 - 2.97 [ P ≤ .01 ] ) . In addition , 4 years of fosinopril treatment result ed in a risk reduction of 45 % ( 95 % CI 6%-75 % [ P = .04 ] ) in this group compared with placebo . Subjects originally assigned to pravastatin had no overall risk reduction in the primary end point ( P = .99 ) . CONCLUSIONS Elevated UAE is associated with increased cardiovascular mortality and morbidity after 9.5 years of follow-up , with a doubling of the risk if the UAE is > 50 mg per 24 hours . In this group , the benefits of 4-year treatment with fosinopril were sustained during posttrial follow-up for cardiovascular mortality and morbidity . We propose that UAE be used to estimate risk in the general population and that large clinical trials be design ed to confirm the hypothesis that angiotensin-converting enzyme-inhibitor treatment may be beneficial in patients with mildly elevated UAE despite the absence of other comorbidities Background The PROspect i ve Study of Pravastatin in the Elderly at Risk ( PROSPER ) , a placebo-controlled trial of pravastatin , demonstrated a 19 % reduction in coronary outcomes ( p = 0.006 ) after a mean of 3.2 years , with no impact on stroke outcomes or all-cause mortality . However , there was a suggestion of increased cancer risk . Our aim is to determine the long-term benefits and safety of pravastatin treatment in older people using post-trial follow-up of the PROSPER participants . Methods 5,804 ( 2,520 Scottish ) men and women aged 70–82 years with either pre-existing vascular disease or increased risk of such disease because of smoking , hypertension or diabetes , were r and omised to 40 mg pravastatin or matching placebo . Using record linkage to routinely collected health records , all participants ( full cohort ) were linked to death and cancer registries , and the Scottish cohort additionally to hospital admissions , to provide composite fatal/non-fatal cardiovascular outcomes ( total mean follow-up 8.6 years ) . Results Pravastatin treatment for 3.2 years reduced CHD death in the full cohort , hazard ratio ( HR ) 0.80 , 95 % confidence interval ( CI ) 0.68–0.95 , p = 0.0091 and fatal coronary events or coronary hospitalisations in the Scottish cohort ( HR 0.81 , 95 % CI 0.69–0.95 , p = 0.0081 ) over 8.6 years . There was no reduction in stroke or all-cause mortality . Cancer risk was not increased in the full cohort ( HR 1.08 , 95 % CI 0.96–1.21 , p = 0.22 ) . Conclusions Pravastatin treatment of elderly high-risk subjects for 3.2 years provided long-term protection against CHD events and CHD mortality . However , this was not associated with any increase in life expectancy , possibly due to competing mortality with deaths from other causes . There was no evidence of long-term increased risk of cancer . Trial registration IS RCT N40976937 BACKGROUND Post-trial monitoring of patients in the United Kingdom Prospect i ve Diabetes Study ( UKPDS ) examined whether risk reductions for microvascular and macrovascular disease , achieved with the use of improved blood-pressure control during the trial , would be sustained . METHODS Among 5102 UKPDS patients with newly diagnosed type 2 diabetes mellitus , we r and omly assigned , over a 4-year period beginning in 1987 , 1148 patients with hypertension to  tight or less-tight blood-pressure control regimens .  The 884 patients who underwent post-trial monitoring  were asked to attend annual UKPDS clinics for the first 5 years , but no attempt was made to maintain their previously assigned therapies . Annual question naires completed by patients and general practitioners were used to follow patients who were unable to attend the clinic in years 1 through 5 , and question naires were used for all patients in years 6 to 10 . Seven prespecified aggregate clinical end points were examined on an intention-to-treat basis , according to the previous r and omization categories . RESULTS Differences in blood pressure between the two groups during the trial disappeared within 2 years after termination of the trial . Significant relative risk reductions found during the trial for any diabetes-related end point , diabetes-related death , microvascular disease , and stroke in the group receiving tight , as compared with less tight , blood-pressure control were not sustained during the post-trial follow-up . No risk reductions were seen during or after the trial for myocardial infa rct ion or death from any cause , but a risk reduction for peripheral vascular disease associated with tight blood-pressure control became significant ( P=0.02 ) . CONCLUSIONS The benefits of previously improved blood-pressure control were not sustained when between-group differences in blood pressure were lost . Early improvement in blood-pressure control in patients with both type 2 diabetes and hypertension was associated with a reduced risk of complications , but it appears that good blood-pressure control must be continued if the benefits are to be maintained . ( UKPDS 81 ; Current Controlled Trials number , IS RCT N75451837 . BACKGROUND Treatment with angiotensin-converting-enzyme ( ACE ) inhibitors reduces mortality among survivors of acute myocardial infa rct ion , but whether to use ACE inhibitors in all patients or only in selected patients is uncertain . METHODS We screened 6676 consecutive patients with 7001 myocardial infa rct ions confirmed by enzyme studies . A total of 2606 patients had echocardiographic evidence of left ventricular systolic dysfunction ( ejection fraction , < or = 35 percent ) . On days 3 to 7 after infa rct ion , 1749 patients were r and omly assigned to receive oral tr and olapril ( 876 patients ) or placebo ( 873 patients ) . The duration of follow-up was 24 to 50 months . RESULTS During the study period , 304 patients ( 34.7 percent ) in the tr and olapril group died , as compared with 369 ( 42.3 percent ) in the placebo group ( P = 0.001 ) . The relative risk of death in the tr and olapril group , as compared with the placebo group , was 0.78 ( 95 percent confidence interval , 0.67 to 0.91 ) . Tr and olapril also reduced the risk of death from cardiovascular causes ( relative risk , 0.75 ; 95 percent confidence interval , 0.63 to 0.89 ; P = 0.001 ) and sudden death ( relative risk , 0.76 ; 95 percent confidence interval , 0.59 to 0.98 ; P = 0.03 ) . Progression to severe heart failure was less frequent in the tr and olapril group ( relative risk , 0.71 ; 95 percent confidence interval , 0.56 to 0.89 ; P = 0.003 ) . In contrast , the risk of recurrent myocardial infa rct ion ( fatal or nonfatal ) was not significantly reduced ( relative risk , 0.86 ; 95 percent confidence interval , 0.66 to 1.13 ; P = 0.29 ) . CONCLUSIONS Long-term treatment with tr and olapril in patients with reduced left ventricular function soon after myocardial infa rct ion significantly reduced the risk of overall mortality , mortality from cardiovascular causes , sudden death , and the development of severe heart failure . That mortality was reduced in a r and omized study enrolling 25 percent of consecutive patients screened should encourage the selective use of ACE inhibition after myocardial infa rct ion BACKGROUND Although statins reduce coronary and cerebrovascular morbidity and mortality in middle-aged individuals , their efficacy and safety in elderly people is not fully established . Our aim was to test the benefits of pravastatin treatment in an elderly cohort of men and women with , or at high risk of developing , cardiovascular disease and stroke . METHODS We did a r and omised controlled trial in which we assigned 5804 men ( n=2804 ) and women ( n=3000 ) aged 70 - 82 years with a history of , or risk factors for , vascular disease to pravastatin ( 40 mg per day ; n=2891 ) or placebo ( n=2913 ) . Baseline cholesterol concentrations ranged from 4.0 mmol/L to 9.0 mmol/L. Follow-up was 3.2 years on average and our primary endpoint was a composite of coronary death , non-fatal myocardial infa rct ion , and fatal or non-fatal stroke . Analysis was by intention-to-treat . FINDINGS Pravastatin lowered LDL cholesterol concentrations by 34 % and reduced the incidence of the primary endpoint to 408 events compared with 473 on placebo ( hazard ratio 0.85 , 95 % CI 0.74 - 0.97 , p=0.014 ) . Coronary heart disease death and non-fatal myocardial infa rct ion risk was also reduced ( 0.81 , 0.69 - 0.94 , p=0.006 ) . Stroke risk was unaffected ( 1.03 , 0.81 - 1.31 , p=0.8 ) , but the hazard ratio for transient ischaemic attack was 0.75 ( 0.55 - 1.00 , p=0.051 ) . New cancer diagnoses were 
    Output:
    