***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 and Purpose — After stroke and transient ischemic attack there is a high early risk of recurrent stroke , particularly in large artery disease . It has been suggested more intensive antiplatelet regimens are required , but trial data are lacking . Treatment efficacy can be evaluated using transcranial Doppler detection of embolic signals . Ambulatory transcranial Doppler has recently been developed ; prolonged recording may reduce subject numbers required to determine therapeutic efficacy . In a r and omized trial ( IS RCT N68019845 ) with blinded end point evaluation , we determined whether treatment with dipyridamole or clopidogrel , in addition to aspirin , was more effective at reducing embolization . Methods — Consecutive patients with recent symptomatic carotid stenosis were recruited . Ambulatory transcranial Doppler and platelet aggregometry were performed at baseline and 48 hours . Patients , all on aspirin , were r and omized to dipyridamole or clopidogrel . Recordings were analyzed offline masked to subject identity . Results — Sixty patients were recruited , 30 in each arm . The primary end point of change in embolic signal frequency did not differ between groups ( P=0.36 ) . In patients with embolic signals at baseline , there was no difference in reduction in embolic signal frequency  : dipyridamole ( 75.5 ; SD 17.7 % ) versus clopidogrel ( 77.5 ; SD 20.5 % ; P=0.77 ) . Baseline platelet aggregation was not different between regimens , but at 48 hours , adenosine 5′-diphosphate aggregation rate ( but not collagen ) was lower with clopidogrel ( P<0.001 ) . Conclusions — Both dipyridamole and clopidogrel  reduced embolization to a similar extent . Embolic signals are strong predictors of future stroke rate in this patient group . Our results suggest these 2 treatment regimens have similar efficacy in early secondary prevention of stroke , although this now needs testing in large Phase III trials Background and Purpose — An optimal strategy for management of symptomatic intracranial atherosclerotic stenosis ( ICAS ) has not yet been established . We compared the efficacy of 2 combinations of antiplatelets , aspirin plus cilostazol ( cilostazol group ) verus aspirin plus clopidogrel ( clopidogrel group ) , on the progression of ICAS , which is known to be associated with clinical stroke recurrence . Methods — In this investigator-initiated double-blind trial , 457 patients with acute symptomatic stenosis in the M1 segment of the middle cerebral artery or the basilar artery were r and omly allocated into either a cilostazol group or a clopidogrel group . After 7 months of treatment , follow-up MR angiogram and MRI were performed . The primary end point was the progression of ICAS in comparison with stenosis on the baseline MR angiogram . Secondary end points included the occurrence of new ischemic lesions on MRI , composite of cardiovascular events , and major bleeding complications . Results — Cardiovascular events occurred in 15 of 232 patients ( 6.4 % ) in the cilostazol group and 10 of 225 ( 4.4 % ) in the clopidogrel group ( P=0.312 ) . Cilostazol did not reduce the progression of symptomatic ICAS ( 20 of 202 ) compared to clopidogrel ( 32 of 207 ) ( odds ratio , 0.61 ; P=0.092 ) , although favorable changes in serum lipoproteins were observed in the cilostazol group . There were no significant differences between the 2 groups with respect to new ischemic lesions ( 18.7 % versus 12.0 % ; P=0.078 ) and major hemorrhagic complications ( 0.9 % versus 2.6 % ; P=0.163 ) . Conclusions — This trial failed to show significant difference in preventing progression of ICAS and new ischemic lesions between the 2 combination antiplatelet therapies in the patients with symptomatic ICAS . Clinical Trial Registration — URL : http://www . clinical trials.gov . Unique identifier : NCT00130039 Background : Different aspects of acute stroke management and strategies for stroke prevention derive from two viewpoints : specific traditional and historical background s and evidence -based medicine from modern r and omized controlled trials ( RCTs ) , meta- analysis and authorized clinical practice guidelines ( GLs ) . Regarding stroke , GLs have been published by national and international organizations in different language s , most frequently in English . Cerebrovascular Diseases published the European GLs for the management of ischemic stroke and transient ischemic attacks in 2003 , with an up date in 2008 . At about the same time ( in 2004 ) , the first Japanese GLs for the management of stroke appeared in Japanese . The first English version of the up date d Japanese GLs was published only in 2011 and included differently approved drugs and drug dosages as compared with other American or European countries . Methods : Since 2011 , the authors have met repeatedly and have compared the latest versions of published European and Japanese GLs for ischemic and hemorrhagic strokes . Many aspects have only been addressed in one but left out in the other GLs , which consequently founded the basis for the comparison . Classification of evidence levels and recommendation grade s defined by the individual committees differed between both original GLs . Results : Aspects of major importance were surprisingly similar and hence did not need extensive interpretation . Other aspects of ischemic stroke management differed significantly , e.g. the dosage of recombinant tissue plasminogen activator  approved in Japan is lower ( 0.6 mg/kg ) than in Europe ( 0.9 mg/kg ) , which derived from different practice s in cardiovascular treatment prior to the design of acute ischemic stroke RCTs . Furthermore , comedication with neuroprotective agents ( edaravone ) , intravenous anticoagulants ( argatroban ) or antiplatelet agents within 1 - 2 days after stroke onset is recommended in Japan but not in Europe . For cardioembolic stroke prevention , a major difference consists in a higher international normalized ratio target ( 2.0 - 3.0 ) in younger subjects versus in those > 70 years ( 1.6 - 2.6 ) , without age restrictions in Europe . Conclusion : This brief survey - when compared with the lengthy original recommendations - provides a stimulating basis for an extended interest among Japanese and European stroke clinicians to learn from their individual experiences and to strengthen efforts for joint cooperation in treating and preventing stroke all around the globe 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 
    Output:
    
Conclusions : Compared with monotherapy , short-term aspirin in combination with clopidogrel is more effective as secondary prevention of stroke or TIA without increasing the risk of hemorrhagic stroke and major bleeding events .
Long-term combination therapy does not reduce the risk of stroke recurrence , and is associated with increased major bleeding events .