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 Patients with transient ischaemic attack ( TIA ) or minor stroke are at high immediate risk of stroke . The optimum early treatment options for these patients are not known . METHODS Within 24 h of symptom onset , we r and omly assigned , in a factorial design , 392 patients with TIA or minor stroke to clopidogrel  ( 300 mg loading dose then 75 mg daily ; 198 patients ) or placebo ( 194 patients ) , and simvastatin ( 40 mg daily ; 199 patients ) or placebo ( 193 patients ) . All patients were also given aspirin and were followed for 90 days . Descriptive analyses were done by intention to treat . The primary outcome was total stroke ( ischaemic and haemorrhagic ) within 90 days . Safety outcomes included haemorrhage related to clopidogrel and myositis related to simvastatin . This study is registered as an International St and ard R and omised Controlled Trial ( number 35624812 ) and with Clinical Trials.gov ( NCT00109382 ) . FINDINGS The median time to stroke outcome was 1 day ( range 0 - 62 days ) . The trial was stopped early due to a failure to recruit patients at the prespecified minimum enrolment rate because of increased use of statins . 14 ( 7.1 % ) patients on clopidogrel had a stroke within 90 days compared with 21 ( 10.8 % ) patients on placebo ( risk ratio 0.7 [ 95 % CI 0.3 - 1.2 ] ; absolute risk reduction -3.8 % [ 95 % CI -9.4 to 1.9 ] ; p=0.19 ) . 21 ( 10.6 % ) patients on simvastatin had a stroke within 90 days compared with 14 ( 7.3 % ) patients on placebo ( risk ratio 1.3 [ 0.7 - 2.4 ] ; absolute risk increase 3.3 % [ -2.3 to 8.9 ] ; p=0.25 ) . The interaction between clopidogrel and simvastatin was not significant ( p=0.64 ) . Two patients on clopidogrel had intracranial haemorrhage compared with none on placebo ( absolute risk increase 1.0 % [ -0.4 to 2.4 ] ; p=0.5 ) . There was no difference between groups for the simvastatin safety outcomes . INTERPRETATION Immediately after TIA or minor stroke , patients are at high risk of stroke , which might be reduced by using clopidogrel in addition to aspirin . The haemorrhagic risks of the combination of aspirin and clopidogrel do not seem to offset this potential benefit . We were unable to provide evidence of benefit of simvastatin in this setting . This aggressive prevention approach merits further study 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 more frequent on pravastatin than on placebo ( 1.25 , 1.04 - 1.51 , p=0.020 ) . However , incorporation of this finding in a meta- analysis of all pravastatin and all statin trials showed no overall increase in risk . Mortality from coronary disease fell by 24 % ( p=0.043 ) in the pravastatin group . Pravastatin had no significant effect on cognitive function or disability . INTERPRETATION Pravastatin given for 3 years reduced the risk of coronary disease in elderly individuals . PROSPER therefore extends to elderly individuals the treatment strategy currently used in middle aged people A total of 462 patients ( mean age 52 years ) affected by reversible focal ischemic attacks ( RIAs ) were followed prospect ively in 8 neurologic institutions in Italy for 4 years . All cases were evaluated with a cerebral angiography and 21 % of angiograms were normal . At the end of the follow-up period the cumulated probability for death , stroke , cardiac event and new RIA was respectively 7 % , 8 % , 3 % and 36 % . The predictive value of the baseline characteristics of this series was evaluated by a multifactorial analysis which showed that RIA and stroke ( specific cerebrovascular risk ) were more likely to develop in patients with a history of more than one RIA and in those in whom multiple vascular territories were involved . Moreover , previous myocardial infa rct ion , intermittent claudication , angina pectoris , time elapsed since the first attack , and duration and severity of the attack itself were independently associated with general cardiovascular risk ( death , stroke and myocardial infa rct ion ) . We conclude that predictive factors , and thus also pathogenetic mechanisms , may be different for general cardiovascular risk and specific cerebrovascular risk in RIA patients BACKGROUND The lowering of cholesterol concentrations in individuals at high risk of cardiovascular disease improves outcome . No study , however , has assessed benefits of cholesterol lowering in the primary prevention of coronary heart disease ( CHD ) in hypertensive patients who are not conventionally deemed dyslipidaemic . METHODS Of 19342 hypertensive patients ( aged 40 - 79 years with at least three other cardiovascular risk factors ) r and omised to one of two antihypertensive regimens in the Anglo-Sc and inavian Cardiac Outcomes Trial , 10305 with non-fasting total cholesterol concentrations 6.5 mmol/L or less were r and omly assigned additional atorvastatin 10 mg or placebo .  These patients formed the lipid-lowering arm of the study . We planned follow-up for an average of 5 years , the primary endpoint being non-fatal myocardial infa rct ion and fatal CHD . Data were analysed by intention to treat . FINDINGS Treatment was stopped after a median follow-up of 3.3 years . By that time , 100 primary events had occurred in the atorvastatin group compared with 154 events in the placebo group ( hazard ratio 0.64 [ 95 % CI 0.50 - 0.83 ] , p=0.0005 ) . This benefit emerged in the first year of follow-up . There was no significant heterogeneity among prespecified subgroups . Fatal and non-fatal stroke ( 89 atorvastatin vs 121 placebo , 0.73 [ 0.56 - 0.96 ] , p=0.024 ) , total cardiovascular events ( 389 vs 486 , 0.79 [ 0.69 - 0.90 ] , p=0.0005 ) , and total coronary events ( 178 vs 247 , 0.71 [ 0.59 - 0.86 ] , p=0.0005 ) were also significantly lowered . There were 185 deaths in the atorvastatin group and 212 in the placebo group ( 0.87 [ 0.71 - 1.06 ] , p=0.16 ) . Atorvastatin lowered total serum cholesterol by about 1.3 mmol/L compared with placebo at 12 months , and by 1.1 mmol/L after 3 years of follow-up . INTERPRETATION The reductions in major cardiovascular events with atorvastatin are large , given the short follow-up time . These findings may have implication s for future lipid-lowering guidelines ABSTRACT — The long‐term prognosis and quality of life of 201 patients admitted to hospital with reversible ischemic attacks ( RIA ) were estimated in a prospect i ve study . The median follow‐up time was 58 months . Further RIAs were reported by 91 patients ( 45 % ) and 48 ( 24 % ) suffered a stroke . The risk of stroke was markedly higher in the first 6 months after RIA , after which the annual stroke rate was rather constant with an average of 4.8 % , about 8 times higher than expected . The average annual mortality rate for the RIA patients was 5.9 % , which is significantly higher than expected . Cardiovascular deaths accounted for more than half of all deaths , stroke for one fourth . Life‐table analysis of subgroups disclosed a much more favorable prognosis for women under 60 years .  High systolic blood pressure , diabetes , and previous myocardial infa rct ion were identified as risk factors . The occurrence of RIA had significantly influenced the quality of life and occupational status for the majority of the patients , even for those who did not suffer a subsequent stroke . Decreased working capacity , general asthenia and fatigue and impaired memory were the most common complaints . We conclude that RIA may be a more serious vascular event than generally believed . Apart from carrying a substantial risk of stroke and death , even a single RIA can cause permanent psychological dysfunction influencing the quality of life BACKGROUND The role of lipid modification in stroke prevention is controversial , although increasing evidence suggests that HMG-CoA reductase inhibition may reduce cerebrovascular events in patients with prevalent coronary artery disease . METHODS AND RESULTS To test the hypothesis that cholesterol reduction with pravastatin may reduce stroke incidence after myocardial infa rct ion , we followed 4159 subjects with average total and LDL serum cholesterol levels ( mean , 209 and 139 mg/dL , respectively ) who had sustained an infa rct ion an average of 10 months before study entry and who were r and omized to pravastatin 40 mg/d or placebo in the Cholesterol and Recurrent Events ( CARE ) trial . Using prospect ively defined criteria , we assessed the incidence of stroke , a prespecified secondary end point , and transient ischemic attack ( TIA ) over a median 5-year follow-up period . Patients were well matched for stroke risk factors and the use of antiplatelet agents ( 85 % of subjects in each group ) . Compared with placebo , pravastatin lowered total serum cholesterol by 20 % , LDL cholesterol by 32 % , and triglycerides by 14 % and raised HDL cholesterol by 5 % over the course of the trial . A total of 128 strokes ( 52 on pravastatin , 76 on placebo ) and 216 strokes or TIAs ( 92 on pravastatin , 124 on placebo ) were observed , representing a 32 % reduction ( 95 % CI , 4 % to 52 % , P=0.03 ) in all-cause stroke and 27 % reduction in stroke or TIA ( 95 % CI , 4 % to 44 % , P=0.02 ) . All categories of strokes were reduced , and treatment effect was similar when adjusted for age , sex , history of hypertension , cigarette smoking , diabetes , left ventricular ejection fraction , and baseline total , HDL , and LDL cholesterol and triglyceride levels . There was no increase in hemorrhagic stroke in patients on pravastatin compared with placebo ( 2 versus 6 , respectively ) . CONCLUSIONS Pravastatin significantly reduced stroke and stroke or TIA incidence after myocardial infa rct ion in patients with average serum cholesterol levels despite the high concurrent use of antiplatelet therapy BACKGROUND AND PURPOSE Rebleeding in patients with primary intracerebral hemorrhage is considered uncommon , but there are no precise data to support this opinion . The purpose of this study was to assess the incidence and predictors of recurrent bleeding in survivors of primary intracerebral hemorrhage . METHODS As part of a prospect i ve study , 112 survivors of a first primary intracerebral hemorrhage were followed up for a mean period of 84.1 months after their discharge . To ascertain risk factors that may influence rebleeding , several demographic , medical history , clinical , and laboratory variables were collected and analyzed . RESULTS Twenty-four percent ( 27/112 ) of survivors experienced one or more rebleeding during the follow-up period , in 8 cases ( 30 % 
    Output:
    
agent
There is evidence that statin therapy in patients with a history of ischaemic stroke or TIA significantly reduces subsequent major coronary events but only marginally reduces the risk of stroke recurrence .
There is no clear evidence of beneficial effect from statins in those with previous haemorrhagic stroke and it is unclear whether statins should be started immediately post stroke or later .
***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 Patients with transient ischaemic attack ( TIA ) or minor stroke are at high immediate risk of stroke . The optimum early treatment options for these patients are not known . METHODS Within 24 h of symptom onset , we r and omly assigned , in a factorial design , 392 patients with TIA or minor stroke to clopidogrel  ( 300 mg loading dose then 75 mg daily ; 198 patients ) or placebo ( 194 patients ) , and simvastatin ( 40 mg daily ; 199 patients ) or placebo ( 193 patients ) . All patients were also given aspirin and were followed for 90 days . Descriptive analyses were done by intention to treat . The primary outcome was total stroke ( ischaemic and haemorrhagic ) within 90 days . Safety outcomes included haemorrhage related to clopidogrel and myositis related to simvastatin . This study is registered as an International St and ard R and omised Controlled Trial ( number 35624812 ) and with Clinical Trials.gov ( NCT00109382 ) . FINDINGS The median time to stroke outcome was 1 day ( range 0 - 62 days ) . The trial was stopped early due to a failure to recruit patients at the prespecified minimum enrolment rate because of increased use of statins . 14 ( 7.1 % ) patients on clopidogrel had a stroke within 90 days compared with 21 ( 10.8 % ) patients on placebo ( risk ratio 0.7 [ 95 % CI 0.3 - 1.2 ] ; absolute risk reduction -3.8 % [ 95 % CI -9.4 to 1.9 ] ; p=0.19 ) . 21 ( 10.6 % ) patients on simvastatin had a stroke within 90 days compared with 14 ( 7.3 % ) patients on placebo ( risk ratio 1.3 [ 0.7 - 2.4 ] ; absolute risk increase 3.3 % [ -2.3 to 8.9 ] ; p=0.25 ) . The interaction between clopidogrel and simvastatin was not significant ( p=0.64 ) . Two patients on clopidogrel had intracranial haemorrhage compared with none on placebo ( absolute risk increase 1.0 % [ -0.4 to 2.4 ] ; p=0.5 ) . There was no difference between groups for the simvastatin safety outcomes . INTERPRETATION Immediately after TIA or minor stroke , patients are at high risk of stroke , which might be reduced by using clopidogrel in addition to aspirin . The haemorrhagic risks of the combination of aspirin and clopidogrel do not seem to offset this potential benefit . We were unable to provide evidence of benefit of simvastatin in this setting . This aggressive prevention approach merits further study 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 more frequent on pravastatin than on placebo ( 1.25 , 1.04 - 1.51 , p=0.020 ) . However , incorporation of this finding in a meta- analysis of all pravastatin and all statin trials showed no overall increase in risk . Mortality from coronary disease fell by 24 % ( p=0.043 ) in the pravastatin group . Pravastatin had no significant effect on cognitive function or disability . INTERPRETATION Pravastatin given for 3 years reduced the risk of coronary disease in elderly individuals . PROSPER therefore extends to elderly individuals the treatment strategy currently used in middle aged people A total of 462 patients ( mean age 52 years ) affected by reversible focal ischemic attacks ( RIAs ) were followed prospect ively in 8 neurologic institutions in Italy for 4 years . All cases were evaluated with a cerebral angiography and 21 % of angiograms were normal . At the end of the follow-up period the cumulated probability for death , stroke , cardiac event and new RIA was respectively 7 % , 8 % , 3 % and 36 % . The predictive value of the baseline characteristics of this series was evaluated by a multifactorial analysis which showed that RIA and stroke ( specific cerebrovascular risk ) were more likely to develop in patients with a history of more than one RIA and in those in whom multiple vascular territories were involved . Moreover , previous myocardial infa rct ion , intermittent claudication , angina pectoris , time elapsed since the first attack , and duration and severity of the attack itself were independently associated with general cardiovascular risk ( death , stroke and myocardial infa rct ion ) . We conclude that predictive factors , and thus also pathogenetic mechanisms , may be different for general cardiovascular risk and specific cerebrovascular risk in RIA patients BACKGROUND The lowering of cholesterol concentrations in individuals at high risk of cardiovascular disease improves outcome . No study , however , has assessed benefits of cholesterol lowering in the primary prevention of coronary heart disease ( CHD ) in hypertensive patients who are not conventionally deemed dyslipidaemic . METHODS Of 19342 hypertensive patients ( aged 40 - 79 years with at least three other cardiovascular risk factors ) r and omised to one of two antihypertensive regimens in the Anglo-Sc and inavian Cardiac Outcomes Trial , 10305 with non-fasting total cholesterol concentrations 6.5 mmol/L or less were r and omly assigned additional atorvastatin 10 mg or placebo .  These patients formed the lipid-lowering arm of the study . We planned follow-up for an average of 5 years , the primary endpoint being non-fatal myocardial infa rct ion and fatal CHD . Data were analysed by intention to treat . FINDINGS Treatment was stopped after a median follow-up of 3.3 years . By that time , 100 primary events had occurred in the atorvastatin group compared with 154 events in the placebo group ( hazard ratio 0.64 [ 95 % CI 0.50 - 0.83 ] , p=0.0005 ) . This benefit emerged in the first year of follow-up . There was no significant heterogeneity among prespecified subgroups . Fatal and non-fatal stroke ( 89 atorvastatin vs 121 placebo , 0.73 [ 0.56 - 0.96 ] , p=0.024 ) , total cardiovascular events ( 389 vs 486 , 0.79 [ 0.69 - 0.90 ] , p=0.0005 ) , and total coronary events ( 178 vs 247 , 0.71 [ 0.59 - 0.86 ] , p=0.0005 ) were also significantly lowered . There were 185 deaths in the atorvastatin group and 212 in the placebo group ( 0.87 [ 0.71 - 1.06 ] , p=0.16 ) . Atorvastatin lowered total serum cholesterol by about 1.3 mmol/L compared with placebo at 12 months , and by 1.1 mmol/L after 3 years of follow-up . INTERPRETATION The reductions in major cardiovascular events with atorvastatin are large , given the short follow-up time . These findings may have implication s for future lipid-lowering guidelines ABSTRACT — The long‐term prognosis and quality of life of 201 patients admitted to hospital with reversible ischemic attacks ( RIA ) were estimated in a prospect i ve study . The median follow‐up time was 58 months . Further RIAs were reported by 91 patients ( 45 % ) and 48 ( 24 % ) suffered a stroke . The risk of stroke was markedly higher in the first 6 months after RIA , after which the annual stroke rate was rather constant with an average of 4.8 % , about 8 times higher than expected . The average annual mortality rate for the RIA patients was 5.9 % , which is significantly higher than expected . Cardiovascular deaths accounted for more than half of all deaths , stroke for one fourth . Life‐table analysis of subgroups disclosed a much more favorable prognosis for women under 60 years .  High systolic blood pressure , diabetes , and previous myocardial infa rct ion were identified as risk factors . The occurrence of RIA had significantly influenced the quality of life and occupational status for the majority of the patients , even for those who did not suffer a subsequent stroke . Decreased working capacity , general asthenia and fatigue and impaired memory were the most common complaints . We conclude that RIA may be a more serious vascular event than generally believed . Apart from carrying a substantial risk of stroke and death , even a single RIA can cause permanent psychological dysfunction influencing the quality of life BACKGROUND The role of lipid modification in stroke prevention is controversial , although increasing evidence suggests that HMG-CoA reductase inhibition may reduce cerebrovascular events in patients with prevalent coronary artery disease . METHODS AND RESULTS To test the hypothesis that cholesterol reduction with pravastatin may reduce stroke incidence after myocardial infa rct ion , we followed 4159 subjects with average total and LDL serum cholesterol levels ( mean , 209 and 139 mg/dL , respectively ) who had sustained an infa rct ion an average of 10 months before study entry and who were r and omized to pravastatin 40 mg/d or placebo in the Cholesterol and Recurrent Events ( CARE ) trial . Using prospect ively defined criteria , we assessed the incidence of stroke , a prespecified secondary end point , and transient ischemic attack ( TIA ) over a median 5-year follow-up period . Patients were well matched for stroke risk factors and the use of antiplatelet agents ( 85 % of subjects in each group ) . Compared with placebo , pravastatin lowered total serum cholesterol by 20 % , LDL cholesterol by 32 % , and triglycerides by 14 % and raised HDL cholesterol by 5 % over the course of the trial . A total of 128 strokes ( 52 on pravastatin , 76 on placebo ) and 216 strokes or TIAs ( 92 on pravastatin , 124 on placebo ) were observed , representing a 32 % reduction ( 95 % CI , 4 % to 52 % , P=0.03 ) in all-cause stroke and 27 % reduction in stroke or TIA ( 95 % CI , 4 % to 44 % , P=0.02 ) . All categories of strokes were reduced , and treatment effect was similar when adjusted for age , sex , history of hypertension , cigarette smoking , diabetes , left ventricular ejection fraction , and baseline total , HDL , and LDL cholesterol and triglyceride levels . There was no increase in hemorrhagic stroke in patients on pravastatin compared with placebo ( 2 versus 6 , respectively ) . CONCLUSIONS Pravastatin significantly reduced stroke and stroke or TIA incidence after myocardial infa rct ion in patients with average serum cholesterol levels despite the high concurrent use of antiplatelet therapy BACKGROUND AND PURPOSE Rebleeding in patients with primary intracerebral hemorrhage is considered uncommon , but there are no precise data to support this opinion . The purpose of this study was to assess the incidence and predictors of recurrent bleeding in survivors of primary intracerebral hemorrhage . METHODS As part of a prospect i ve study , 112 survivors of a first primary intracerebral hemorrhage were followed up for a mean period of 84.1 months after their discharge . To ascertain risk factors that may influence rebleeding , several demographic , medical history , clinical , and laboratory variables were collected and analyzed . RESULTS Twenty-four percent ( 27/112 ) of survivors experienced one or more rebleeding during the follow-up period , in 8 cases ( 30 % 
    Output:
    