***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 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 The PFA-100 system is a platelet function analyzer design ed to measure platelet-related primary hemostasis . The instrument uses two disposable cartridges : a collagen/epinephrine ( CEPI ) and a collagen/ADP ( CADP ) cartridge . Previous experience has shown that CEPI cartridges detect qualitative platelet defects , including acetylsalicylic acid (ASA)-induced abnormalities , while CADP cartridges detect only thrombocytopathies and not ASA use . In this seven-center trial , 206 healthy subjects and 176 persons with various platelet-related defects , including 127 ASA users , were studied . The platelet function status was determined by a platelet function test panel . Comparisons were made as to how well the defects were identified by the PFA-100 system and by platelet aggregometry . The reference intervals for both cartridges , testing the 206 healthy subjects , were similar to values described in smaller studies in the literature [ mean closure time ( CT ) 132 s for CEPI and 93 s for CADP ] . The use of different lot numbers of cartridges or duplicate versus singleton testing revealed no differences . Compared with the platelet function status , the PFA-100 system had a clinical sensitivity of 94.9 % and a specificity of 88.8 % . For aggregometry , a sensitivity of 94.3 % and a specificity of 88.3 % were obtained . These values are based on all 382 specimens . A separate analysis of sensitivity by type of platelet defect , ASA use versus congenital thrombocytopathies , revealed for the PFA-100 system a 94.5 % sensitivity in identifying ASA users and a 95.9 % sensitivity in identifying the other defects . For aggregometry , the values were 100 % for ASA users and 79.6 % for congenital defects . Analysis of concordance between the PFA-100 system and aggregometry revealed no difference in clinical sensitivity and specificity between the systems ( p > 0.9999 ) . The overall agreement was 87.5 % , with a Kappa index of 0.751 . The two tests are thus equivalent in their ability to identify normal and abnormal platelet defects .  Testing 126 subjects who took 325 mg ASA revealed that the PFA-100 system ( CEPI ) was able to detect 71.7 % of ASA-induced defects with a positive predictive value of 97.8 % . The overall clinical accuracy of the system , calculated from the area under the ROC curve , was 0.977 . The data suggest that the PFA-100 system is highly accurate in discriminating normal from abnormal platelet function . The ease of operation of the instrument makes it a useful tool to use in screening patients for platelet-related hemostasis defects Background and Purpose — The annual risk of ischemic stroke distal to ≥50 % asymptomatic carotid stenoses was ≈2 % to 3 % in early cohort studies and subsequent r and omized trials of endarterectomy . This risk might have fallen in recent years owing to improvements in medical treatment , but there are no published prognostic data from studies initiated within the last 10 years . Methods — In a population -based study of all patients with transient ischemic attack ( TIA ) or stroke in the Oxford Vascular Study , we studied the risk of TIA and stroke in patients with ≥50 % contralateral asymptomatic carotid stenoses recruited consecutively from 2002 to 2009 and given intensive contemporary medical treatment .  Results — Of 1153 consecutively imaged patients presenting with stroke or TIA , 101 ( 8.8 % ) had ≥50 % asymptomatic carotid stenoses ( mean age , 75 years ; 39 % women ; 40 % age ≥80 years ) . During 301 patient-years of follow-up ( mean , 3 years ) , there were 6 ischemic events in the territory of an asymptomatic stenosis , 1 minor stroke ( initially 50 % to 69 % stenosis ) , and 5 TIAs ( 2 initially 50 % to 69 % stenosis ; 3 to 70 % to 99 % stenosis ) , 3 of which led to subsequent endarterectomy . The average annual event rates on medical treatment were 0.34 % ( 95 % CI , 0.01 to 1.87 ) for any ipsilateral ischemic stroke , 0 % ( 95 % CI , 0.00 to 0.99 ) for disabling ipsilateral stroke , and 1.78 % ( 95 % CI , 0.58 to 4.16 ) for ipsilateral TIA . Conclusions — In the first study of the prognosis of ≥50 % asymptomatic carotid stenosis to be initiated in the last 10 years , the risk of stroke on intensive contemporary medical treatment was low . Larger studies are required to determine whether this apparent improvement in prognosis is generalizable 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 Background —Postoperative thromboembolic stroke affects 2 % to 3 % of patients undergoing carotid endarterectomy ( CEA ) and is preceded by 1 to 2 hours of increasing cerebral embolization . Previous work has demonstrated that high rates of postoperative embolization are associated with increased platelet reactivity to adenosine 5′-diphosphate ( ADP ) . Our hypothesis was that preoperative administration of the platelet ADP antagonist clopidogrel could reduce postoperative embolization . Methods and Results —One hundred CEA patients on routine aspirin therapy ( 150 mg ) were r and omized to 75 mg clopidogrel ( n=46 
    Output:
    
Furthermore , pilot data suggest that platelet activation may be increased in recently symptomatic than in asymptomatic severe carotid stenosis .
Excessive platelet activation and platelet hyperreactivity may play a role in the pathogenesis of first or subsequent transient ischemic attack or stroke in patients with moderate or severe carotid stenosis .