***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 — 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 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 Aspirin , dipyridamole and clopidogrel are effective in secondary vascular prevention . Combination therapy with three antiplatelet agents might maximise the benefit of antiplatelet treatment  in the secondary prevention of ischaemic stroke . Methodology /Principal Findings A r and omised , parallel group , observer-blinded phase II trial compared the combination of aspirin , clopidogrel and dipyridamole with aspirin alone .  Adult patients with ischaemic stroke or transient ischaemic attack ( TIA ) within 5 years were included . The primary outcome was tolerability to treatment assessed as the number of patients completing r and omised treatment . Recruitment was halted prematurely after publication of the ESPRIT trial ( which confirmed that combined aspirin and dipyridamole is more effective than aspirin alone ) . 17 patients were enrolled : male 12 ( 71 % ) , mean age 62 ( SD 13 ) years , lacunar stroke syndrome 12 ( 71 % ) , median stroke/TIA onset to r and omisation 8 months . Treatment was discontinued in 4 of 9 ( 44 % ) patients receiving triple therapy vs. none of 8 taking aspirin ( p = 0.08 ) . One recurrent stroke occurred in a patient in the triple group who was noncompliant of all antiplatelet medications . The number of patients with adverse events and bleeding complications , and their severity , were significantly greater in the triple therapy group ( p<0.01 ) . Conclusions / Significance Long term triple antiplatelet therapy was asociated with a significant increase in adverse events and bleeding rates , and their severity , and a trend to increased discontinuations . However , the patients had a low risk of recurrence and future trials should focus on short term therapy in high risk patients characterised by a very recent event or failure of dual antiplatelet therapy . Trial Registration Controlled-Trials.com IS RCT 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 Short course of dual antiplatelet therapy for early secondary prevention is a promising treatment for patients with minor stroke or transient ischemic attack at high risk of recurrence . Methods We examined the efficacy and safety of dual antiplatelets in patients with transient ischemic attack or minor stroke , defined as National Institute of Health Stroke Scale scores 0–3 , in a subgroup analysis of Clopidogrel plus aspirin versus Aspirin alone for Reducing embolization in patients with acute symptomatic cerebral or carotid artery stenosis ( CLAIR ) study .  Microembolic signals on transcranial Doppler monitoring was used as surrogate marker for recurrent stroke risk . 
    Output:
    
Nevertheless , short- duration DAPT ( ≤ 1 month ) started during the early acute ischemic phase was associated with less bleeding than longer DAPT and greater reduction of recurrent strokes compared with monotherapy .
In contrast , long DAPT and DAPT started later after the index event ( ≥ 1 month ) were associated with similar rates of any stroke and increased risks of bleeding compared with monotherapy .
Similar findings were observed in patients who presented with minor stroke/TIA .
Conclusions : Among patients who presented with ischemic stroke/TIA , short-course clopidogrel plus aspirin immediately following the index event appears to be more effective than and as safe as monotherapy for secondary stroke prevention