***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 Summary Background Intensive antiplatelet therapy with three agents might be more effective than guideline treatment for preventing recurrent events in patients with acute cerebral ischaemia . We aim ed to compare the safety and efficacy of intensive antiplatelet therapy ( combined aspirin , clopidogrel , and dipyridamole ) with that of guideline -based antiplatelet therapy . Methods We did an international , prospect i ve , r and omised , open-label , blinded-endpoint trial in adult participants with ischaemic stroke or transient ischaemic attack ( TIA ) within 48 h of onset . Participants were assigned in a 1:1 ratio using computer r and omisation to receive loading doses and then 30 days of intensive antiplatelet therapy ( combined aspirin 75 mg , clopidogrel 75 mg , and dipyridamole 200 mg twice daily ) or guideline -based therapy ( comprising either clopidogrel alone or combined aspirin and dipyridamole ) . R and omisation was stratified by country and index event , and minimised with prognostic baseline factors , medication use , time to r and omisation , stroke-related factors , and thrombolysis . The ordinal primary outcome was the combined incidence and severity of any recurrent stroke ( ischaemic or haemorrhagic ; assessed using the modified Rankin Scale ) or TIA within 90 days , as assessed by central telephone follow-up with masking to treatment assignment , and analysed by intention to treat . This trial is registered with the IS RCT N registry , number IS RCT N47823388 . Findings 3096 participants ( 1556 in the intensive antiplatelet therapy group , 1540 in the guideline antiplatelet therapy group ) were recruited from 106 hospitals in four countries between April 7 , 2009 , and March 18 , 2016 . The trial was stopped early on the recommendation of the data monitoring committee . The incidence and severity of recurrent stroke or TIA did not differ between intensive and guideline therapy ( 93 [ 6 % ] participants vs 105 [ 7 % ] ; adjusted common odds ratio [ cOR ] 0·90 , 95 % CI 0·67–1·20 , p=0·47 ) . By contrast , intensive antiplatelet therapy was associated with more , and more severe , bleeding ( adjusted cOR 2·54 , 95 % CI 2·05–3·16 , p<0·0001 ) . Interpretation Among patients with recent cerebral ischaemia  , intensive antiplatelet therapy did not reduce the incidence and severity of recurrent stroke or TIA , but did significantly increase the risk of major bleeding . Triple antiplatelet therapy should not be used in routine clinical practice . Funding National Institutes of Health Research Health Technology Assessment Programme , British Heart Foundation BACKGROUND Few r and omised clinical trials have investigated the use of antithrombotic drugs for early secondary prevention of stroke or transient ischaemic attack in patients with intracranial atherosclerotic stenosis . Microembolic signals , detected by transcranial doppler , are a surrogate marker of future stroke risk and have been used to show treatment efficacy in patients with extracranial carotid stenosis . We aim ed to investigate whether treatment with clopidogrel plus aspirin reduced the number of microembolic signals detected with transcranial doppler ultrasound compared with aspirin alone in patients with recent stroke . METHODS The clopidogrel plus aspirin for infa rct ion reduction in acute stroke or transient ischaemic attack patients with large artery stenosis and microembolic signals ( CLAIR ) trial was a r and omised , open-label , blinded-endpoint trial . Between Oct 28 , 2003 , and Nov 19 , 2008 , patients with acute ischaemic stroke or transient ischaemic attack who had symptomatic large artery stenosis in the cerebral or carotid arteries and in whom microembolic signals were present on transcranial doppler were r and omly assigned within 7 days of symptom onset to receive clopidogrel ( 300 mg for the first day , then 75 mg daily ) plus aspirin ( 75 - 160 mg daily ) or aspirin alone ( 75 - 160 mg daily ) for 7 days . Patients were r and omly assigned in blocks of four or six by use of a r and omisation website . Monitoring of microembolic signals on transcranial doppler was done on days 2 and 7 . The primary endpoint was the proportion of patients who had microembolic signals on day 2 . Analysis was by modified intention to treat . All analyses were done by an investigator masked to both patient identity and the day the recording was taken . This trial is registered with the Centre for Clinical Trials , Chinese University of Hong Kong , number CUHK_CCT00164 . FINDINGS 100 patients were r and omly assigned to clopidogrel plus aspirin ( n=47 ) or aspirin monotherapy ( n=53 ) . 93 of 100 patients had symptomatic intracranial stenosis in either the intracranial internal carotid artery or the middle cerebral artery : 45 of 46 in the dual therapy group and 48 of 52 in the monotherapy group . At day 2 , 14 of 45 patients in the dual therapy group and 27 of 50 patients in the monotherapy group for whom data were available had at least one microembolic signal on transcranial doppler ( relative risk reduction 42.4 % , 95 % CI 4.6 - 65.2 ; p=0.025 ) . Adverse events were similar in the two groups . No patients had intracranial or severe systemic haemorrhage , but two patients in the dual therapy group had minor haemorrhages . INTERPRETATION Combination therapy with clopidogrel and aspirin is more effective than aspirin alone in reducing microembolic signals in patients with predominantly intracranial symptomatic stenosis . Clinical trials are now warranted to investigate whether this combination treatment also results in a reduction in stroke incidence Background — Evidence for efficacy of dual antiplatelet therapy in stroke is limited . Symptomatic carotid stenosis patients are at high risk of early recurrent stroke . In this group , asymptomatic microembolic signals ( MES ) , detected by transcranial Doppler ultrasound ( TCD ) , are markers of future stroke and transient ischemic attack ( TIA ) risk . They offer a surrogate marker to evaluate antiplatelet therapy , but no multicenter study has evaluated the feasibility of this approach . Methods and Results —Clopidogrel and Aspirin for Reduction of Emboli in Symptomatic Carotid Stenosis ( CARESS ) is a r and omized , double-blind study in subjects with recently symptomatic ≥50 % carotid stenosis . Patients were screened with TCD , and if MES were detected , they were r and omized to clopidogrel and aspirin or aspirin monotherapy . Repeated TCD recordings were made on days 2 and 7 . MES were detected in 110 of 230 patients by online analysis at baseline , of whom 107 were r and omized . Intention-to-treat analysis revealed a significant reduction in the primary end point : 43.8 % of dual-therapy patients were MES positive on day 7 , as compared with 72.7 % of monotherapy patients ( relative risk reduction 39.8 % ; 95 % CI , 13.8 to 58.0 ; P=0.0046 ) . The secondary end point of MES frequency per hour was reduced ( compared with baseline ) by 61.4 % ( 95 % CI , 31.6 to 78.2 ; P=0.0013 ) in the dual-therapy group at day 7 and by 61.6 % ( 95 % CI , 34.9 to 77.4 ; P=0.0005 ) on day 2 . There were 4 recurrent strokes and 7 TIAs in the monotherapy group versus no stroke and 4 TIAs in the dual-therapy group that were treatment emergent and ipsilateral to the qualifying carotid stenosis ; 2 additional ipsilateral TIAs occurred before treatment started . MES frequency was greater in the 17 patients with recurrent ipsilateral events compared with the 90 without ( mean±SD : 24.4±27.7 versus 8.9±11.5 per hour ; P=0.0003 ) . Conclusions —In patients with recently symptomatic carotid stenosis , combination therapy with clopidogrel and aspirin is more effective than aspirin alone in reducing asymptomatic embolization . Doppler MES detection is a feasible method to evaluate the efficacy of antiplatelet therapy in multicenter studies Purpose — The aim of this guideline is to provide a focused up date of the current recommendations for the  endovascular  treatment of  acute ischemic stroke . When there is overlap , the recommendations made here supersede those of previous guidelines . Methods — This focused up date analyzes results from 8 r and omized , clinical trials of endovascular treatment and other relevant data published since 2013 . It is not intended to be a complete literature review from the date of the previous guideline publication but rather to include pivotal new evidence that justifies changes in current recommendations . Members of the writing committee were appointed by the American Heart Association/American Stroke Association Stroke Council ’s Scientific Statement Oversight Committee and the American Heart Association/American Stroke Association Manuscript Oversight Committee . Strict adherence to the American Heart Association conflict of interest policy was maintained throughout the consensus process . Recommendations follow the American Heart Association/American Stroke Association methods of classifying the level of certainty of the treatment effect and the class of evidence . Prerelease review of the draft guideline was performed by 6 expert peer review ers and by the members of the Stroke Council Scientific Statement Oversight Committee and Stroke Council Leadership Committee . Results — Evidence -based guidelines are presented for the selection of patients with acute ischemic stroke for endovascular treatment , for the endovascular procedure , and for systems of care to facilitate endovascular treatment . Conclusions — Certain endovascular procedures have been demonstrated to provide clinical benefit in selected patients with acute ischemic stroke . Systems of care should be organized to facilitate the delivery of this care 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 (  
    Output:
    
Conclusions Among patients with acute non-cardioembolic IS or TIA within 3 days of ictus , dual antiplatelet therapy was associated with a reduction in stroke recurrence , and composite vascular events , when compared with monotherapy .
However , a significant increase in the risk of major bleeding was observed