***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 assess the effect of more intensive medical therapy on the rate of transcranial Doppler ( TCD ) microemboli and cardiovascular events in patients with asymptomatic carotid stenosis ( ACS ) . DESIGN A prospect i ve study . SETTING A teaching hospital . PATIENTS Four hundred sixty-eight patients with ACS greater than 60 % by Doppler peak velocity . MAIN OUTCOME MEASURES We compared ( 1 ) the proportion of ACS patients who had microemboli on TCD  , ( 2 ) cardiovascular events , ( 3 ) rate of carotid plaque progression , and ( 4 )  baseline medical therapy  , before and since 2003 . RESULTS Among 468 ACS patients , 199 were enrolled between January 1 , 2000 , and December 31 , 2002 ; and 269 were enrolled between January 1 , 2003 , and July 30 , 2007 .  Microemboli were present in 12.6 % before 2003 and 3.7 % since 2003 ( P < .001 ) . The decline in microemboli coincided with better control of plasma lipids and slower progression of carotid total plaque area . Since 2003 , there have been significantly fewer cardiovascular events among patients with ACS : 17.6 % had stroke , death , myocardial infa rct ion , or carotid endarterectomy for symptoms before 2003 , vs 5.6 % since 2003 ( P < .001 ) . The rate of carotid plaque progression in the first year of follow-up has declined from 69 mm(2 ) ( SD , 96 mm(2 ) ) to 23 mm(2 ) ( SD , 86 mm(2 ) ) ( P < .001 ) . CONCLUSIONS Cardiovascular events and microemboli on TCD have markedly declined with more intensive medical therapy . Less than 5 % of patients with ACS now st and to benefit from revascularization ; patients with ACS should receive intensive medical therapy and should only be considered for revascularization if they have microemboli on TCD Background and Purpose — This study aim ed to monitor  cognitive performance  during a 3-year period in subjects with bilateral asymptomatic severe internal carotid artery stenosis and to explore the role of cerebral hemodynamics and atherosclerotic disease in the development of cognitive dysfunction . Methods — One hundred fifty-nine subjects with bilateral asymptomatic severe internal carotid artery stenosis were included and prospect ively evaluated for a 3-year period . At entry , demographics , vascular risk profile , and pharmacological treatments were defined .  Cognitive status  was evaluated using the  Mini-Mental State Examination at baseline and at follow-up .  Cerebral hemodynamics was assessed by transcranial Doppler – based breath-holding index test . As a measure of the extent of systemic atherosclerotic disease , common carotid artery intima-media thickness was measured . A cutoff for pathological values was set at 0.69 for breath-holding index and 1.0 mm for intima-media thickness . Results — The risk of decreasing in Mini-Mental State Examination score increased progressively from patients with bilaterally normal to those with unilaterally abnormal breath-holding index , reaching the highest probability in patients with bilaterally abnormal breath-holding index ( P<0.0001 ) . Pathological values of intima-media thickness did not influence the risk of Mini-Mental State Examination score change . Conclusions — Our findings suggest that patients with asymptomatic bilateral severe internal carotid artery stenosis may be at risk of developing cognitive impairment . The evaluation of the hemodynamic status , besides providing insights about the possible mechanism behind the cognitive dysfunction present in carotid atherosclerotic disease , may be of help for the individuation of subjects deserving earlier and more aggressive treatments Background and Purpose — Progression of asymptomatic carotid stenoses with > 50 % luminal narrowing is associated with an increased risk of stroke . The significance of the progression rate in these patients is unknown . The main aim of this study was to evaluate the rate of change of carotid luminal narrowing over 1 year , as a risk factor for ipsilateral ischemic events , in patients with a > 50 % asymptomatic carotid stenosis . Secondary aims were to establish the incidence of changes in carotid luminal narrowing and establish additional risk factors for ipsilateral neurological events . Methods — A retrospective analysis was conducted of data derived from the deferred endarterectomy arm of the Asymptomatic Carotid Surgery Trial . Patients were followed up for ≥5 years with serial carotid duplex examinations . Data were derived from information obtained at r and omization and annual follow-up visits with carotid duplex examination . Potential risk factors for ipsilateral neurological events were analyzed in Poisson regression models . Results — Data from 1469 patients were included . Two hundred forty-four had ipsilateral events ; 240 had ipsilateral carotid surgery ; 370 died from nonstroke causes ; and 82 had an asymptomatic carotid occlusion . The annual incidence of progression in the cohort as a whole was 5.2 % . Ipsilateral events occurred in 17 % of patients . Diabetes and previous contralateral symptoms showed a significant independent association with ipsilateral neurological events . Ipsilateral events were associated with high rates of progression over 1 year but not with low progression rates or regression . Conclusions — Fast rates of progression of carotid luminal narrowing should be interpreted as a sign of significantly increased risk of future ipsilateral neurological events BACKGROUND Previous clinical trials have suggested that carotid-artery stenting with a device to capture and remove emboli ( " embolic protection " ) is an effective alternative to carotid endarterectomy in patients at average or high risk for surgical complications . METHODS In this trial , we compared carotid-artery stenting with embolic protection and carotid endarterectomy in patients 79 years of age or younger who had severe carotid stenosis and were asymptomatic ( i.e. , had not had a stroke , transient ischemic attack , or amaurosis fugax in the 180 days before enrollment ) and were not considered to be at high risk for surgical complications . The trial was design ed to enroll 1658 patients but was halted early , after 1453 patients underwent r and omization , because of slow enrollment . Patients were followed for up to 5 years . The primary composite end point of death , stroke , or myocardial infa rct ion within 30 days after the procedure or ipsilateral stroke within 1 year was tested at a noninferiority margin of 3 percentage points . RESULTS Stenting was noninferior to endarterectomy with regard to the primary composite end point ( event rate , 3.8 % and 3.4 % , respectively ; P=0.01 for noninferiority ) . The rate of stroke or death within 30 days was 2.9 % in the stenting group and 1.7 % in the endarterectomy group ( P=0.33 ) . From 30 days to 5 years after the procedure , the rate of freedom from ipsilateral stroke was 97.8 % in the stenting group and 97.3 % in the endarterectomy group ( P=0.51 ) , and the overall survival rates were 87.1 % and 89.4 % , respectively ( P=0.21 ) . The cumulative 5-year rate of stroke-free survival was 93.1 % in the stenting group and 94.7 % in the endarterectomy group ( P=0.44 ) . CONCLUSIONS In this trial involving asymptomatic patients with severe carotid stenosis who were not at high risk for surgical complications , stenting was noninferior to endarterectomy with regard to the rate of the primary composite end point at 1 year . In analyses that included up to 5 years of follow-up , there were no significant differences between the study groups in the rates of non-procedure-related stroke , all stroke , and survival . ( Funded by Abbott Vascular ; ACT I Clinical Trials.gov number , NCT00106938 . ) BACKGROUND For an asymptomatic patient with severe carotid stenosis the most important question is how to prevent an ischemic stroke . Carotid artery stenosis is the estimated cause of stroke in 8 - 20 % of the cases . Today more than 50 % of procedures for carotid stenosis are done on asymptomatic patients , but few of the r and omized controlled trials comparing carotid endarterectomy and stenting examined specifically these patients . METHODS All patients with severe ( > 70 % ) asymptomatic carotid artery stenosis seen in the Carmel medical center vascular clinic were prospect ively screened and r and omized 1:1 for carotid endarterectomy ( CEA ) or carotid stenting ( CAS ) .  Patients eligible for both procedures were enrolled . The primary objectives of the study were : 1 ) periprocedural complications - stroke ( CVA ) , transient ischemic attack ( TIA ) , myocardial infa rct ion ( MI ) , and death ; 2 ) long-term results : mortality , prevention of ipsilateral stroke or TIA , and freedom from restenosis . RESULTS One-hundred and thirty-six patients were treated with mean follow-up of 26 months . There was no difference in short and long term results between the two groups . Thirty day morbidity included : 1 CVA in each group with no MI . Long-term results included 4 deaths in each group ; none from CVA . One TIA was noted after CAS , and 3 cases of restenosis were found in CEA and one in CAS . CONCLUSIONS CAS is a maturing procedure and has improved significantly over the past several years . Future developments of stents and protection devices will achieve better perioperative results . This along with our excellent long term results will promote the use of stenting for suitable patients OBJECTIVES This study determines the risk of ipsilateral ischaemic neurological events in relation to the degree of asymptomatic carotid stenosis and other risk factors . METHODS Patients ( n=1115 ) with asymptomatic internal carotid artery ( ICA ) stenosis greater than 50 % in relation to the bulb diameter were followed up for a period of 6 - 84 ( mean 37.1 ) months . Stenosis was grade d using duplex , and clinical and biochemical risk factors were recorded . RESULTS The relationship between ICA stenosis and event rate is linear when stenosis is expressed by the ECST method , but S-shaped if expressed by the NASCET method . In addition to the ECST grade of stenosis ( RR 1.6 ; 95 % CI 1.21 - 2.15 ) , history of contralateral TIAs ( RR 3.0 ; 95 % CI 1.90 - 4.73 ) and creatinine in excess of 85 micromol/L ( RR 2.1 ; 95 % CI 1.23 - 3.65 ) were independent risk predictors . The combination of these three risk factors can identify a high-risk group ( 7.3 % annual event rate and 4.3 % annual stroke rate ) and a low risk group ( 2.3 % annual event rate and 0.7 % annual stroke rate ) . CONCLUSIONS Linearity between ECST per cent stenosis and risk makes this method for grading stenosis more amenable to risk prediction without any transformation not only in clinical practice but also when multivariable analysis is to be used . Identification of additional risk factors provides a new approach to risk stratification and should help refine the indications for carotid endarterectomy BACKGROUND Because of recent advances in best medical treatment ( BMT ) , it is currently unclear whether any additional surgical or endovascular interventions confer additional benefit , in terms of preventing late ipsilateral carotid territory ischemic stroke in asymptomatic patients with significant carotid stenoses . The aim was to compare the stroke-preventive effects of BMT alone , with that of BMT in combination with carotid endarterectomy ( CEA ) or carotid artery stenting ( CAS ) in patients with high grade asymptomatic extracranial carotid artery stenosis . METHODS SPACE-2 was planned as a three-armed , r and omized controlled trial ( BMT alone vs. CEA plus BMT vs. CAS plus BMT , IS RCT N 78592017 ) . However , because of slow patient recruitment , the three-arm study design was amended ( July 2013 ) to become two parallel r and omized studies ( BMT alone vs. CEA plus BMT , and BMT alone vs. CAS plus BMT ) . RESULTS The change in study design did not lead to any significant increase in patient recruitment , and trial recruitment ceased after recruiting 513 patients over a 5 year period ( CEA vs. BMT ( n = 203 ) ; CAS vs. BMT ( n = 197 ) , and BMT alone ( n = 113 ) ) . The 30 day rate of death/stroke was 1.97 % for patients undergoing CEA , and 2.54 % for patients undergoing CAS . No strokes or deaths occurred in the first 30 days after r and omization in patients r and omized to BMT . There were several potential reasons for the low recruitment rates into SPACE-2 , including the ability for referring doctors to refer their patients directly for CEA or CAS outwith the trial , an inability to convince patients ( who had come " mentally prepared " that an intervention was necessary ) 
    Output:
    
A recent review has , however , identified a number of clinical /imaging features that may be associated with higher rates of stroke on medical therapy .
Summary The majority of surgeons/interventionists are unlikely to accept radical changes in practice until new r and omized trials confirm that the risk of stroke on modern medical therapy is significantly lower than that previously accepted .