***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 To determine the incremental cost-effectiveness of clopidogrel plus aspirin ( C + A ) compared with aspirin ( A ) alone during the Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization , Management and Avoidance ( CHARISMA ) trial from a US payer perspective . BACKGROUND Although the CHARISMA trial did not find a benefit of adding clopidogrel to aspirin in its overall study cohort , a benefit was suggested in a prespecified subgroup of patients with established cardiovascular ( CV ) disease . The cost-effectiveness of dual antiplatelet therapy in this population is unknown . METHODS Medical re source utilization was assessed prospect ively , and costs for hospitalizations , physician services , outpatient care , and medications were assigned using 2007 US dollars . Life expectancy was estimated contingent on fatal and nonfatal CV events using statistical models of long-term survival from the Saskatchewan Health data base . RESULTS C + A was associated with a 12.5 % relative reduction in CV death , myocardial infa rct ion , or stroke compared with A alone ( 6.9 % vs. 7.9 % , P = 0.048 ) over a median 28 months of follow-up . Severe or moderate bleeding events were higher in patients receiving C + A versus A alone ( 3.6 % vs. 2.5 % , P < 0.001 ) . Mean cost/patient was $ 2607 higher for C + A , while projected life expectancy increased by an average of 0.072 years due to fewer in-trial events . The result ing incremental cost-effectiveness ratio ( ICER ) for C + A was $ 36,343/year of life gained . Findings were insensitive to discount rate , life expectancy projections , post-event costs , and indirect costs from lost productivity ; the ICER was most sensitive to the cost of clopidogrel . Bootstrap analysis demonstrated that the ICER for C + A remained < $ 50,000/life-year gained in 70.6 % of bootstrap replicates and < $ 100,000/life-year gained in 87.4 % . CONCLUSIONS Among patients with established CV disease , adding clopidogrel to aspirin appears to increase life expectancy modestly at a cost generally considered acceptable within the US health-care system Background — The Clopidogrel in High-risk patients with Acute Non-disabling Cerebrovascular Events ( CHANCE ) trial showed that the combined treatment of clopidogrel and aspirin decreases the 90-day risk of stroke without increasing hemorrhage in comparison with aspirin alone , but provided insufficient data to establish whether the benefit persisted over a longer period of time beyond the trial termination . We report the 1-year follow-up outcomes of this trial . Methods and Results — The trial was a r and omized , double-blind ,  placebo-controlled trial conducted at 114 centers in China . We r and omly assigned 5170 patients within 24 hours after onset of minor stroke or high-risk transient ischemic attack to clopidogrel-aspirin therapy ( loading dose of 300 mg of clopidogrel on day 1 , followed by 75 mg of clopidogrel per day for 90 days , plus 75 mg of aspirin per day for the first 21 days ) or to the aspirin-alone group ( 75 mg/d for 90 days ) . The primary outcome was stroke event ( ischemic or hemorrhagic ) during 1-year follow-up . Differences in outcomes between groups were assessed by using the Cox proportional hazards model . Stroke occurred in 275 ( 10.6 % ) patients in the clopidogrel-aspirin group , in comparison with 362 ( 14.0 % ) patients in the aspirin group ( hazard ratio , 0.78 ; 95 % confidence interval , 0.65–0.93 ; P=0.006 ) . Moderate or severe hemorrhage occurred in 7 ( 0.3 % ) patients in the clopidogrel-aspirin group and in 9 ( 0.4 % ) patients in the aspirin group ( P=0.44 ) . Conclusions — The early benefit of clopidogrel-aspirin treatment in reducing the risk of subsequent stroke persisted for the duration of 1-year of follow-up . Clinical Trial Registration — URL : http://www . clinical trials.gov . Unique identifier : NCT00979589 Summary Background Lifelong antiplatelet treatment is recommended after ischaemic vascular events , on the basis of trials done mainly in patients younger than 75 years .  Upper gastrointestinal bleeding is a serious complication , but had low case fatality in trials of aspirin and is not generally thought to cause long-term disability . Consequently , although co-prescription of proton-pump inhibitors ( PPIs ) reduces upper gastrointestinal bleeds by 70–90 % , uptake is low and guidelines are conflicting . We aim ed to assess the risk , time course , and outcomes of bleeding on antiplatelet treatment for secondary prevention in patients of all ages . Methods We did a prospect i ve population -based cohort study in patients with a first transient ischaemic attack , ischaemic stroke , or myocardial infa rct ion treated with antiplatelet drugs ( mainly aspirin based , without routine PPI use ) after the event in the Oxford Vascular Study from 2002 to 2012 , with follow-up until 2013 . We determined type , severity , outcome ( disability or death ) , and time course of bleeding requiring medical attention by face-to-face follow-up for 10 years . We estimated age-specific numbers needed to treat ( NNT ) to prevent upper gastrointestinal bleeding with routine PPI co-prescription on the basis of Kaplan – Meier risk estimates and relative risk reduction estimates from previous trials . Findings 3166 patients ( 1582 [ 50 % ] aged ≥75 years ) had 405 first bleeding events ( n=218 gastrointestinal , n=45 intracranial , and n=142 other ) during 13 509 patient-years of follow-up . Of the 314 patients ( 78 % ) with bleeds admitted to hospital , 117 ( 37 % ) were missed by administrative coding . Risk of non-major bleeding was unrelated to age , but major bleeding increased steeply with age ( ≥75 years hazard ratio [ HR ] 3·10 , 95 % CI 2·27–4·24 ; p<0·0001 ) , particularly for fatal bleeds ( 5·53 , 2·65–11·54 ; p<0·0001 ) , and was sustained during long-term follow-up . The same was true of major upper gastrointestinal bleeds ( ≥75 years HR 4·13 , 2·60–6·57 ; p<0·0001 ) , particularly if disabling or fatal ( 10·26 , 4·37–24·13 ; p<0·0001 ) . At age 75 years or older , major upper gastrointestinal bleeds were mostly disabling or fatal ( 45 [ 62 % ] of 73 patients vs 101 [ 47 % ] of 213 patients with recurrent ischaemic stroke ) , and outnumbered disabling or fatal intracerebral haemorrhage ( n=45 vs n=18 ) , with an absolute risk of 9·15 ( 95 % CI 6·67–12·24 ) per 1000 patient-years . The estimated NNT for routine PPI use to prevent one disabling or fatal upper gastrointestinal bleed over 5 years fell from 338 for individuals younger than 65 years , to 25 for individuals aged 85 years or older . Interpretation In patients  receiving aspirin-based antiplatelet treatment  without routine PPI use , the long-term risk of major bleeding is higher and more sustained in older patients in practice than in the younger patients in previous trials , with a substantial risk of disabling or fatal upper gastrointestinal bleeding . Given that half of the major bleeds in patients aged 75 years or older were upper gastrointestinal , the estimated NNT for routine PPI use to prevent such bleeds is low , and co-prescription should be encouraged . Funding Wellcome Trust , Wolfson Foundation , British Heart Foundation , Dunhill Medical Trust , National Institute of Health Research ( NIHR ) , and the NIHR Oxford Biomedical Research Centre BACKGROUND Clopidogrel was superior to aspirin in patients with previous manifestations of atherothrombotic disease in the CAPRIE study and its benefit was amplified in some high-risk subgroups of patients . We aim ed to assess whether addition of aspirin to clopidogrel could have a greater benefit than clopidogrel alone in prevention of vascular events with potentially higher bleeding risk . METHODS We did a r and omised , double-blind , placebo-controlled trial to compare aspirin ( 75 mg/day ) with placebo in 7599 high-risk patients with recent ischaemic stroke or transient ischaemic attack and at least one additional vascular risk factor who were already receiving clopidogrel 75 mg/day . Duration of treatment and follow-up was 18 months . The primary endpoint was a composite of ischaemic stroke , myocardial infa rct ion , vascular death , or rehospitalisation for acute ischaemia ( including rehospitalisation for transient ischaemic attack , angina pectoris , or worsening of peripheral arterial disease ) . Analysis was by intention to treat , using logrank test and a Cox 's proportional-hazards model . FINDINGS 596 ( 15.7 % ) patients reached the primary endpoint in the group receiving aspirin and clopidogrel compared with 636 ( 16.7 % ) in the clopidogrel alone group ( relative risk reduction 6.4 % , [ 95 % CI -4.6 to 16.3 ] ; absolute risk reduction 1 % [ -0.6 to 2.7 ] ) . Life-threatening bleedings were higher in the group receiving aspirin and clopidogrel versus clopidogrel alone ( 96 [ 2.6 % ] vs 49 [ 1.3 % ] ; absolute risk increase 1.3 % [ 95 % CI 0.6 to 1.9 ] ) . Major bleedings were also increased in the group receiving aspirin and clopidogrel but no difference was recorded in mortality . INTERPRETATION Adding aspirin to clopidogrel in high-risk patients with recent ischaemic stroke or transient ischaemic attack is associated with a non-significant difference in reducing major vascular events . However , the risk of life-threatening or major bleeding is increased by the addition of aspirin BACKGROUND Results of trials of aspirin and dipyridamole combined versus aspirin alone for the secondary prevention of  vascular events after ischaemic stroke of presumed arterial origin are inconsistent . Our aim was to resolve this uncertainty . METHODS We did a r and omised controlled trial in which we assigned patients to aspirin ( 30 - 325 mg daily ) with ( n=1363 ) or without ( n=1376 ) dipyridamole ( 200 mg twice daily ) within 6 months of a transient ischaemic attack or minor stroke of presumed arterial origin . Our primary outcome event was the composite of death from all vascular causes , non-fatal stroke , non-fatal myocardial infa rct ion , or major bleeding complication , whichever happened first . Treatment was open , but auditing of outcome events was blinded . Primary analysis was by intention to treat . This study is registered as an International St and ard R and omised Controlled Trial ( number IS RCT N73824458 ) and with ( NCT00161070 ) . FINDINGS Mean follow-up was 3.5 years ( SD 2.0 ) . Median aspirin dose was 75 mg in both treatment groups ( range 30 - 325 ) ; extended-release dipyridamole was used by 83 % ( n=1131 ) of patients on the combination regimen . Primary outcome events arose in 173 ( 13 % ) patients on aspirin and dipyridamole and in 216 ( 16 % ) on aspirin alone ( hazard ratio 0.80 , 95 % CI 0.66 - 0.98 ; absolute risk reduction 1.0 % per year , 95 % CI 0.1 - 1.8 ) . Addition of the ESPRIT data to the meta- analysis of previous trials result ed in an overall risk ratio for the composite of vascular death , stroke , or myocardial infa rct ion of 0.82 ( 95 % CI 0.74 - 0.91 ) . Patients on aspirin and dipyridamole  discontinued trial medication more often than those on aspirin alone ( 470 vs 184 ) , mainly because of headache . INTERPRETATION The ESPRIT results , combined with the results of previous trials , provide sufficient evidence to prefer the combination regimen of aspirin plus dipyridamole over aspirin alone as antithrombotic therapy after cerebral ischaemia of arterial origin Recent studies have suggested that combination antiplatelet therapy may be superior to monotherapy in the treatment of acute stroke . However , additional prospect i ve studies are needed to confirm this finding . The present trial compared the efficacy and safety of clopidogrel plus aspirin versus aspirin alone in the treatment of non-cardioembolic ischemic stroke within 72 hours of onset . Six hundred and ninety patients aged �� 
    Output:
    
For stroke prevention in elderly patients with IS or TIA , DAPT is superior to aspirin monotherapy but appears to be equivalent to clopidogrel monotherapy , and is accompanied by an increased risk of bleeding .