***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: Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more Objective To determine whether aspirin and antioxidant therapy , combined or alone , are more effective than placebo in reducing the development of cardiovascular events in patients with diabetes mellitus and asymptomatic peripheral arterial disease . Design Multicentre , r and omised , double blind , 2 × 2 factorial , placebo controlled trial . Setting 16 hospital centres in Scotl and , supported by 188 primary care groups . Participants 1276 adults aged 40 or more with type 1 or type 2 diabetes and an ankle brachial pressure index of 0.99 or less but no symptomatic cardiovascular disease . Interventions Daily , 100 mg aspirin tablet plus antioxidant capsule ( n=320 ) , aspirin tablet plus placebo capsule ( n=318 ) , placebo tablet plus antioxidant capsule ( n=320 ) , or placebo tablet plus placebo capsule ( n=318 ) . Main outcome measures Two hierarchical composite primary end points of death from coronary heart disease or stroke , non-fatal myocardial infa rct ion or stroke , or amputation above the ankle for critical limb ischaemia ; and death from coronary heart disease or stroke . Results No evidence was found of any interaction between aspirin and antioxidant . Overall , 116 of 638 primary events occurred in the aspirin groups compared with 117 of 638 in the no aspirin groups ( 18.2 % v 18.3 % ) : hazard ratio 0.98 ( 95 % confidence interval 0.76 to 1.26 ) . Forty three deaths from coronary heart disease or stroke occurred in the aspirin groups compared with 35 in the no aspirin groups ( 6.7 % v 5.5 % ) : 1.23 ( 0.79 to 1.93 ) . Among the antioxidant groups 117 of 640 ( 18.3 % ) primary events occurred compared with 116 of 636 ( 18.2 % ) in the no antioxidant groups ( 1.03 , 0.79 to 1.33 ) . Forty two ( 6.6 % ) deaths from coronary heart disease or stroke occurred in the antioxidant groups compared with 36 ( 5.7 % ) in the no antioxidant groups ( 1.21 , 0.78 to 1.89 ) . Conclusion This trial does not provide evidence to support the use of aspirin or antioxidants in primary prevention of cardiovascular events and mortality in the population with diabetes studied . Trial registration Current Controlled Trials IS RCT N53295293 A r and omized , double-blind clinical trial was design ed to assess the effect of aspirin ( ASA ) alone or in combination with dipyridamole ( DIP ) on the patency rates of exp and ed PTFE grafts placed in the infrainguinal position . Forty-nine patients were r and omized into three groups who received three times daily either two placebos ( 17 patients ) , 325 mg ASA and placebo ( 16 patients ) , or 325 mg ASA and 75 mg DIP ( 16 patients ) . The patients were seen at 3-month intervals for 1 year , and coded medication bottles were dispensed and returned pills counted to assess patient compliance . Treatment failure was defined as the first graft occlusion . The data were analyzed using the Breslow statistic for progressively censored survival type data . The 1-year cumulative patency rate for the entire series was 59 % . The rates for above-knee grafts in the ASA group ( 100 % ) and the ASA/DIP group ( 100 % ) were significantly higher than the rates for the placebo group ( 50 % ) ( P = 0.05 ) . The 1-year cumulative patency rates for patients with below-knee grafts were not statistically different among the groups , although the patients who received ASA alone had a higher rate than did the other two groups ( 65 % versus 21 % for placebo and 19 % for ASA/DIP ) . There were fewer occlusions in the above-knee grafts as compared to below-knee grafts in all groups , but the differences were statistically significant only in the ASA/DIP group . There were no statistical differences between the two active treatment groups The effect of 7-mono-hydroxyethylrutoside and its combination with acetylsalicylic acid was evaluated in a controlled clinical trial , performed in 105 patients with obliterative atherosclerosis of the lower limbs , and using non-invasive measurement of peripheral haemodynamic parameters -- blood flow during reactive hyperaemia and ankle systolic blood pressure . Patients , r and omized into three groups , received either placebo or 7-mono-hydroxyethylrutoside alone or in combination with acetylsalicylic acid for 12 months . The placebo group showed a decrease in maximum calf blood flow and a decrease in ankle systolic pressure . Administration of 7-mono-hydroxyethylrutoside did not lead to any significant changes in systolic pressure but there was a decrease in the maximum calf blood flow . There were no statistically significant changes in patients receiving the 7-mono-hydroxyethylrutoside and acetylsalicylic acid combination who , by contrast , showed a tendency to increased values of the parameters measured Thirty one r and omised trials of antiplatelet treatment for patients with a history of transient ischaemic attack , occlusive stroke , unstable angina , or myocardial infa rct ion were identified . Six were still in progress , and the results of the remaining 25 were review ed . They included a total of some 29 000 patients , 3000 of whom had died . Overall , allocation to antiplatelet treatment had no apparent effect on non-vascular mortality but reduced vascular mortality by 15 % ( SD 4 % ) and non-fatal vascular events ( stroke or myocardial infa rct ion ) by 30 % ( 4 % ) . This suggested that with good compliance these treatments might reduce vascular mortality by about one sixth , other vascular events by about a third , and total vascular events by about a quarter . There was no significant difference between the effects of the different types of  antiplatelet treatment tested ( 300 - 325 mg aspirin daily , higher aspirin doses , sulphinpyrazone , or high dose aspirin with dipyridamole ) , nor between the effects in patients with histories of cerebral or cardiac disease . Thus antiplatelet treatment can reduce the incidence of serious vascular events by about a quarter among a wide range of patients at particular risk of occlusive vascular disease . The balance of risk and benefit , however , might be different for “ primary ” prevention among people at low absolute risk of occlusive disease if antiplatelet treatment produced even a small increase in the incidence of cerebral haemorrhage Background : In patients with symptomatic peripheral artery disease with a history of limb revascularization , the optimal antithrombotic regimen for long-term management is unknown . Methods : The EUCLID trial ( Examining Use of Ticagrelor In PAD ) r and omized 13 885 patients with peripheral artery disease to treatment with ticagrelor 90 mg twice daily or clopidogrel 75 mg daily . Patients were enrolled based on an abnormal ankle-brachial index ⩽0.80 or a previous lower extremity revascularization . This analysis focuses on the 7875 ( 57 % ) patients enrolled based on the previous lower extremity revascularization criterion . Patients could not be enrolled within 30 days of most recent revascularization , and patients with an indication for dual antiplatelet therapy were excluded . The primary efficacy end point was a composite of cardiovascular death , myocardial infa rct ion , or ischemic stroke . The primary safety end point was major bleeding . Results : Patients with a previous revascularization had a mean age of 66 years , 73 % were male , and the median baseline ankle-brachial index was 0.78 . After adjustment for baseline characteristics , patients enrolled based on previous revascularization had similar rates of the primary composite end point ( hazard ratio [ HR ] 1.10 , 95 % confidence interval [ CI ] 0.98–1.23 , P=0.12 ) and statistically significantly higher rates of myocardial infa rct ion ( HR 1.29 , 95 % CI 1.08–1.55 , P=0.005 ) and acute limb ischemia ( HR 4.23 , 95 % CI 2.86–6.25 , P<0.001 ) when compared with patients enrolled based on ankle-brachial index criteria . No differences in ticagrelor- versus clopidogrel-treated patients were found for the primary efficacy end point ( 11.4 % vs 11.3 % ; HR 1.01 , 95 % CI 0.88–1.15 ; P=0.90 ) , all-cause mortality ( 9.2 % vs 9.2 % ; HR 0.99 , 95 % CI 0.86–1.15 ; P=0.93 ) , acute limb ischemia ( 2.5 % vs 2.5 % ; HR 1.03 , 95 % CI 0.78–1.36 ; P=0.84 ) , or major bleeding ( 1.9 % vs 1.8 % ; HR 1.15 , 95 % CI 0.83–1.59 ; P=0.41 ) . The median duration of follow-up was ≈30 months . Conclusions : After adjustment for baseline characteristics , patients enrolled based on previous revascularization for peripheral artery disease had higher rates of myocardial infa rct ion and acute limb ischemia , with similar composite rates of cardiovascular death , myocardial infa rct ion , and stroke when compared with patients enrolled based on the ankle-brachial index criterion . No significant differences were found between ticagrelor and clopidogrel for reduction of cardiovascular or acute limb events . Clinical Trial Registration : URL : http://www . clinical trials.gov . Unique identifier : NCT01732822 In this prospect i ve study 364 patients were subjected to different types of arterial reconstructive surgery .  The patients were r and omly divided into four groups according to the type of antithrombotic medication given . During the hospitalization period there were no reocclusions in the dipyridamole/ASA group of 93 patients compared with 12 reocclusions in the control group of 86 patients . The difference was statistically highly significant . The difference between the control group and the given dipyridamole or ASA was not statistically significant .  Dipyridamole and ASA were tolerated well by the patients in this clinical trial . This was the first clinical investigation to prove the effectiveness of dipyridamole and ASA medication in the prevention of reocclusions in arterial reconstructive bypass surgery 240 patients were admitted to a double-blind study to determine the effect of long-term treatment with platelet-function inhibiting agents on occlusive arterial disease in the lower extremities . Patients were r and omised into 1 of 3 treatment groups : aspirin 330 mg ; dipyridamole 75 mg and aspirin 330 mg ; or matching placebo 3 times daily . The duration of treatment was 2 years . Arteriography was carried out at the beginning of the study and 2 years later or before if deterioration was observed . 199 patients completed the study according to the trial protocol . The serial arteriograms were assessed in pairs qualitatively , by means of simple comparative viewing , and semiquantitatively with Bollinger 's score system . Progression of the disease was most pronounced in the placebo-treated group , less so in the aspirin-treated group , and least of all in the dipyridamole- and -aspirin group . Patients who smoke and those with hypertension may benefit most from treatment with the 2 preparations under investigation CONTEXT A low ankle brachial index ( ABI ) indicates atherosclerosis and an increased risk of cardiovascular and cerebrovascular events . Screening for a low ABI can identify an asymptomatic higher risk group potentially amenable to preventive treatments . OBJECTIVE To determine the effectiveness of aspirin in preventing events in people with a low ABI identified on screening the general population . DESIGN , SETTING , AND PARTICIPANTS The Aspirin for Asymptomatic Atherosclerosis trial was an intention-to-treat double-blind r and omized controlled trial conducted from April 1998 to October 2008 , involving 28,980 men and women aged 50 to 75 years living in central Scotl and , free of clinical cardiovascular disease , recruited from a community health registry , and had an ABI screening test . Of those , 3350 with a low ABI ( < or = 0.95 ) were entered into the trial , which was powered to detect a 25 % proportional risk reduction in events . INTERVENTIONS Once daily 100 mg aspirin ( enteric coated ) or placebo . MAIN OUTCOME MEASURES The primary end point was a composite of initial fatal or nonfatal coronary event or 
    Output:
    
CONCLUSIONS Aspirin use in PVD might not be associated with improved cardiovascular outcomes or worse bleeding outcomes .