human
***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: The Persantine Aspirin Trial is a double-blind multi-centered cooperative study focusing primarily on the question of whether the administration of the combination of aspirin and dipyridamole ( Persantine ) will result in a greater reduction of cerebral or retinal infa rct ion or death than the administration of aspirin alone . Fifteen centers in the United States and Canada are participating . More than 750 individuals with a history of recent carotid territory transient ischemic attacks ( TIAs ) have been admitted over the past four years and r and omly allocated to either aspirin ( 325 mg ) plus placebo four times daily or aspirin ( 325 mg ) plus Persantine ( 75 mg ) four times daily . It is anticipated that the study will continue through 1983 . Analysis and publication of results are planned for 1984 604 Patients with atherothrombotic cerebral ischemic events ( transient , 16 % : or completed , 84 % ) referrable either to the carotid or to the vertebral-basilar circulation were entered into a double blind r and omized clinical trial ( AICLA ) to determine whether aspirin ( A ) ( 1 g/day ) or aspirin ( 1 g/day ) + Dipyridamole ( 225 mg/day ) ( AD ) would produce a significant reduction in the subsequent ( 3 years ) occurrence of fatal and nonfatal cerebral infa rct ion . R and omization produced remarkably comparable treatment groups and this good comparability was maintained throughout the study . Adherence to the protocol and drug compliance were excellent . Side effects , particularly symptoms of peptic ulcer and hemorrhagic events were significantly ( p less than 0.03 ) more frequent in the two treatment groups containing aspirin . With the exception of patients who withdrew from the study , each patient was followed for 3 years . At the end of the study , the number of fatal and nonfatal cerebral infa rct ions was 31 in the placebo ( P ) group , 17 in the A group and 18 in the AD group . Taking into account the duration of follow-up for each patient , these figures correspond to cumulative rates of 18 % in the P group and 10.5 % in each of the 2 active treatment groups . Analysis with the Mantel Method showed : 1)--A difference at the 6 % level between the 3 groups and between P and AD ; 2)--A difference at the 5 % level between P and A ; 3)--No difference between ( A and AD ; 4)--A difference at the 2 % level between the P group and the two treated groups taken together ( A + AD ) . Among other diseases occurring during the trial , the only significant difference concerned myocardial infa rct ion , which was less frequent in the 2 treated groups ( P less than 0.05 ) . Subgroup analysis failed to show a significant sex difference in the efficacy of aspirin . It is concluded that , in patients comparable to those defined in the protocol , Aspirin ( 1 g ) has a significantly beneficial effect in the secondary prevention of atherothrombotic cerebral infa rct ion We report the results of a r and omized multicenter clinical trial on the effects of aspirin plus dipyridamole versus placebo on major vascular end points in 231 non-insulin-dependent diabetic men with either a recent amputation for gangrene or active gangrene . Primary end points were death from atherosclerotic vascular disease plus amputation of the opposite extremity for gangrene . There were 24 atherosclerotic deaths in the drug treatment group ( 21.8 % ) and 23 in the placebo group ( 19.0 % ) . There were 22 patients in the drug treatment group ( 20.0 % ) and 29 patients in the placebo group ( 24.0 % ) with opposite-side amputations . Survival curve analyses revealed little difference between these groups for major vascular end points , total mortality , all amputations , or myocardial infa rct ions . The most noteworthy group difference was observed for cerebrovascular end points ( strokes and transient ischemic attacks ) , with an incidence of 8.2 % ( 9 patients ) in the drug treatment group and 19.0 % ( 23 patients ) in the placebo group . We conclude from this study that antiplatelet agents have no effect on the primary vascular end points , vascular deaths and /or amputation of the opposite extremity , in this population . Similarly , no effects were seen on secondary vascular end points , except for a suggestion of protection versus strokes and transient ischemic attacks . However , this finding must be interpreted with caution , since it is a secondary end point and was found only after multiple analyses of the data BACKGROUND Results of trials of aspirin and dipyridamole combined versus aspirin alone for the secondary prevention of  vascular events after ischaemic stroke of presumed arterial origin are inconsistent . Our aim was to resolve this uncertainty . METHODS We did a r and omised controlled trial in which we assigned patients to aspirin ( 30 - 325 mg daily ) with ( n=1363 ) or without ( n=1376 ) dipyridamole ( 200 mg twice daily ) within 6 months of a transient ischaemic attack or minor stroke of presumed arterial origin . Our primary outcome event was the composite of death from all vascular causes , non-fatal stroke , non-fatal myocardial infa rct ion , or major bleeding complication , whichever happened first . Treatment was open , but auditing of outcome events was blinded . Primary analysis was by intention to treat . This study is registered as an International St and ard R and omised Controlled Trial ( number IS RCT N73824458 ) and with ( NCT00161070 ) . FINDINGS Mean follow-up was 3.5 years ( SD 2.0 ) . Median aspirin dose was 75 mg in both treatment groups ( range 30 - 325 ) ; extended-release dipyridamole was used by 83 % ( n=1131 ) of patients on the combination regimen . Primary outcome events arose in 173 ( 13 % ) patients on aspirin and dipyridamole and in 216 ( 16 % ) on aspirin alone ( hazard ratio 0.80 , 95 % CI 0.66 - 0.98 ; absolute risk reduction 1.0 % per year , 95 % CI 0.1 - 1.8 ) . Addition of the ESPRIT data to the meta- analysis of previous trials result ed in an overall risk ratio for the composite of vascular death , stroke , or myocardial infa rct ion of 0.82 ( 95 % CI 0.74 - 0.91 ) . Patients on aspirin and dipyridamole  discontinued trial medication more often than those on aspirin alone ( 470 vs 184 ) , mainly because of headache . INTERPRETATION The ESPRIT results , combined with the results of previous trials , provide sufficient evidence to prefer the combination regimen of aspirin plus dipyridamole over aspirin alone as antithrombotic therapy after cerebral ischaemia of arterial origin In 1988 , we undertook a r and omized , placebo-controlled , double-blind trial to investigate the safety and efficacy of low-dose acetylsalicylic acid ( ASA ) , modified-release dipyridamole , and the two agents in combination for secondary prevention of ischemic stroke . Patients with prior stroke or transient ischemic attack ( TIA ) were r and omized to treatment with ASA alone ( 50 mg daily ) , modified-release dipyridamole alone ( 400 mg daily ) , the two agents in a combined formulation , or placebo . Primary endpoints were stroke , death , and stroke or death together . TIA and other vascular events were secondary endpoints . Patients were followed on treatment for two years . Data from 6,602 patients were analysed . Factorial analysis demonstrated a highly significant effect for ASA and for dipyridamole in reducing the risk of stroke ( p < or = 0.001 ) and stroke or death combined ( p < 0.01 ) . In pairwise comparisons , stroke risk in comparison to placebo was reduced by 18 % with ASA alone ( p = 0.013 ) ; 16 % with dipyridamole alone ( p = 0.039 ) ; and 37 % with combination therapy ( p < 0.001 ) . Risk of stroke or death was reduced by 13 % with ASA alone ( p = 0.016 ) ; 15 % with dipyridamole alone ( p = 0.015 ) ; and 24 % with the combination ( p < 0.001 ) . The treatment had no statistically significant effect on the death rate alone . Factorial analysis also demonstrated a highly significant effect of ASA ( p < 0.001 ) and dipyridamole ( p < 0.01 ) for preventing TIA . The risk reduction for the combination was 36 % ( p < 0.001 ) in comparison with placebo .  Headache was the most common adverse event , occurring more frequently in dipyridamole-treated patients . All-site bleeding and gastrointestinal bleeding were significantly more common in patients who received ASA in comparison to placebo or dipyridamole . We conclude that ( 1 ) ASA 25 mg twice daily and dipyridamole , in a modified-release form , at a dose of 200 mg twice daily have each been shown to be equally effective for the secondary prevention of ischemic stroke and TIA ; ( 2 ) when co-prescribed the protective effects are additive , the combination being significantly more effective than either agent prescribed singly ; ( 3 ) low-dose ASA does not eliminate the propensity for induced bleeding From 1979 - 85 , 2435 patients with a transient ischaemic attack or minor ischaemic stroke were r and omly allocated to receive long term " blind " treatment with aspirin 600 mg twice daily ( n = 815 ) , aspirin 300 mg once daily ( n = 806 ) or placebo ( n = 814 ) . No patient was lost to follow up . The " intention to treat " comparison included all the serious vascular events and deaths which occurred before the end of the follow up period on 30 September 1986 . There was no difference in efficacy between the 300 mg and 1200 mg daily doses of aspirin , but the lower dose was undoubtedly less gastrotoxic . Also , there was no definite difference in the response of  males and females to aspirin . The odds of suffering a major stroke , myocardial infa rct ion or vascular death were 15 % less in the combined aspirin groups compared with the placebo group ( 95 % confidence interval 29 % reduction to 3 % increase in odds ) which is compatible with the continuing overview of all the similar trials of antiplatelet drugs where the relative reduction in odds was 25 % . There was no statistically significant reduction in the likelihood of either disabling major stroke and vascular death or vascular death occurring The effects of dipyridamole in association with acetylsalicylic acid were compared with the effects of acetylsalicylic acid alone in patients with peripheral vascular disease . The following parameters were studied in each patient : symptoms-free interval on the treadmill , ankle-arm arterial pressure gradient , oscillographic index , venous occlusion plethysmography and any untoward reactions . Changes were observed in the pain-free interval ( p less than 0.005 ) , and in the venous occlusion plethysmography ( p less than 0.001 ) in the patients treated with the two drugs in association Since Heberden 's classic description of angina pectoris in 1768 , a satisfactory treatment has been sought . Nitroglycerin , which is the st and ard treatment , may have unpleasant side effects due to vasodilatation , and its duration of action is relatively short . From the rapid turnover of a multitude of alleged long-acting coronary vasodilators marketed , it is apparent that an ideal compound which is both effective and devoid of side effects has not been found . Fischer and Roch reported in 1951 the synthesis of a new group of compounds with two pyrimidine rings . One of these compounds , dipyridamole ( Persantine ) , was subsequently shown to produce a significant increase in coronary blood flow 1 and an increase in intercoronary anastomoses in dogs with surgically induced coronary artery constriction . 2 In patients with angina pectoris , several uncontrolled , or only partially double-blind , studies have indicated that dipyridamole produced subjective improvement . 3 - 6 In contrast , four double-blind studies 7 - 10 have BACKGROUND Oral dipyridamole induces accumulation of endogenous adenosine , which in a hypoxic milieu exerts experimentally an angiogenic effect on coronary collateral circulation . A meta- analysis of 13 r and omized placebo-controlled trials published between 1960 and 1992 showed evidence of benefit for dipyridamole in the treatment of angina pectoris , especially with longer duration of treatment . Aim To assess the efficacy and safety of dipyridamole in the treatment of patients with chronic stable angina in a large scale , international , r and omized , placebo-controlled , parallel group study . METHODS Four hundred patients with chronic stable angina pectoris and a positive treadmill exercise test were r and omized to receive either modified release dipyridamole ( 200 mg b.i.d . p.o . , n=198 ) or corresponding placebo ( n=202 ) , for 24 weeks as an add-on to conventional antianginal therapy and for 4 additional weeks as monotherapy -- the latter after withdrawal of st and ard treatment with calcium antagonists and /or beta-blockers 
    Output:
    
agent
This result was not influenced by the dose of dipyridamole or type of presenting vascular disease .
For patients who presented with arterial vascular disease , there was no evidence that dipyridamole , in the presence or absence of another antiplatelet drug reduced the risk of vascular death , though it reduces the risk of further vascular events .
This benefit was found only in patients presenting after cerebral ischaemia .
There was no evidence that dipyridamole alone was more efficacious than aspirin
***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: The Persantine Aspirin Trial is a double-blind multi-centered cooperative study focusing primarily on the question of whether the administration of the combination of aspirin and dipyridamole ( Persantine ) will result in a greater reduction of cerebral or retinal infa rct ion or death than the administration of aspirin alone . Fifteen centers in the United States and Canada are participating . More than 750 individuals with a history of recent carotid territory transient ischemic attacks ( TIAs ) have been admitted over the past four years and r and omly allocated to either aspirin ( 325 mg ) plus placebo four times daily or aspirin ( 325 mg ) plus Persantine ( 75 mg ) four times daily . It is anticipated that the study will continue through 1983 . Analysis and publication of results are planned for 1984 604 Patients with atherothrombotic cerebral ischemic events ( transient , 16 % : or completed , 84 % ) referrable either to the carotid or to the vertebral-basilar circulation were entered into a double blind r and omized clinical trial ( AICLA ) to determine whether aspirin ( A ) ( 1 g/day ) or aspirin ( 1 g/day ) + Dipyridamole ( 225 mg/day ) ( AD ) would produce a significant reduction in the subsequent ( 3 years ) occurrence of fatal and nonfatal cerebral infa rct ion . R and omization produced remarkably comparable treatment groups and this good comparability was maintained throughout the study . Adherence to the protocol and drug compliance were excellent . Side effects , particularly symptoms of peptic ulcer and hemorrhagic events were significantly ( p less than 0.03 ) more frequent in the two treatment groups containing aspirin . With the exception of patients who withdrew from the study , each patient was followed for 3 years . At the end of the study , the number of fatal and nonfatal cerebral infa rct ions was 31 in the placebo ( P ) group , 17 in the A group and 18 in the AD group . Taking into account the duration of follow-up for each patient , these figures correspond to cumulative rates of 18 % in the P group and 10.5 % in each of the 2 active treatment groups . Analysis with the Mantel Method showed : 1)--A difference at the 6 % level between the 3 groups and between P and AD ; 2)--A difference at the 5 % level between P and A ; 3)--No difference between ( A and AD ; 4)--A difference at the 2 % level between the P group and the two treated groups taken together ( A + AD ) . Among other diseases occurring during the trial , the only significant difference concerned myocardial infa rct ion , which was less frequent in the 2 treated groups ( P less than 0.05 ) . Subgroup analysis failed to show a significant sex difference in the efficacy of aspirin . It is concluded that , in patients comparable to those defined in the protocol , Aspirin ( 1 g ) has a significantly beneficial effect in the secondary prevention of atherothrombotic cerebral infa rct ion We report the results of a r and omized multicenter clinical trial on the effects of aspirin plus dipyridamole versus placebo on major vascular end points in 231 non-insulin-dependent diabetic men with either a recent amputation for gangrene or active gangrene . Primary end points were death from atherosclerotic vascular disease plus amputation of the opposite extremity for gangrene . There were 24 atherosclerotic deaths in the drug treatment group ( 21.8 % ) and 23 in the placebo group ( 19.0 % ) . There were 22 patients in the drug treatment group ( 20.0 % ) and 29 patients in the placebo group ( 24.0 % ) with opposite-side amputations . Survival curve analyses revealed little difference between these groups for major vascular end points , total mortality , all amputations , or myocardial infa rct ions . The most noteworthy group difference was observed for cerebrovascular end points ( strokes and transient ischemic attacks ) , with an incidence of 8.2 % ( 9 patients ) in the drug treatment group and 19.0 % ( 23 patients ) in the placebo group . We conclude from this study that antiplatelet agents have no effect on the primary vascular end points , vascular deaths and /or amputation of the opposite extremity , in this population . Similarly , no effects were seen on secondary vascular end points , except for a suggestion of protection versus strokes and transient ischemic attacks . However , this finding must be interpreted with caution , since it is a secondary end point and was found only after multiple analyses of the data BACKGROUND Results of trials of aspirin and dipyridamole combined versus aspirin alone for the secondary prevention of  vascular events after ischaemic stroke of presumed arterial origin are inconsistent . Our aim was to resolve this uncertainty . METHODS We did a r and omised controlled trial in which we assigned patients to aspirin ( 30 - 325 mg daily ) with ( n=1363 ) or without ( n=1376 ) dipyridamole ( 200 mg twice daily ) within 6 months of a transient ischaemic attack or minor stroke of presumed arterial origin . Our primary outcome event was the composite of death from all vascular causes , non-fatal stroke , non-fatal myocardial infa rct ion , or major bleeding complication , whichever happened first . Treatment was open , but auditing of outcome events was blinded . Primary analysis was by intention to treat . This study is registered as an International St and ard R and omised Controlled Trial ( number IS RCT N73824458 ) and with ( NCT00161070 ) . FINDINGS Mean follow-up was 3.5 years ( SD 2.0 ) . Median aspirin dose was 75 mg in both treatment groups ( range 30 - 325 ) ; extended-release dipyridamole was used by 83 % ( n=1131 ) of patients on the combination regimen . Primary outcome events arose in 173 ( 13 % ) patients on aspirin and dipyridamole and in 216 ( 16 % ) on aspirin alone ( hazard ratio 0.80 , 95 % CI 0.66 - 0.98 ; absolute risk reduction 1.0 % per year , 95 % CI 0.1 - 1.8 ) . Addition of the ESPRIT data to the meta- analysis of previous trials result ed in an overall risk ratio for the composite of vascular death , stroke , or myocardial infa rct ion of 0.82 ( 95 % CI 0.74 - 0.91 ) . Patients on aspirin and dipyridamole  discontinued trial medication more often than those on aspirin alone ( 470 vs 184 ) , mainly because of headache . INTERPRETATION The ESPRIT results , combined with the results of previous trials , provide sufficient evidence to prefer the combination regimen of aspirin plus dipyridamole over aspirin alone as antithrombotic therapy after cerebral ischaemia of arterial origin In 1988 , we undertook a r and omized , placebo-controlled , double-blind trial to investigate the safety and efficacy of low-dose acetylsalicylic acid ( ASA ) , modified-release dipyridamole , and the two agents in combination for secondary prevention of ischemic stroke . Patients with prior stroke or transient ischemic attack ( TIA ) were r and omized to treatment with ASA alone ( 50 mg daily ) , modified-release dipyridamole alone ( 400 mg daily ) , the two agents in a combined formulation , or placebo . Primary endpoints were stroke , death , and stroke or death together . TIA and other vascular events were secondary endpoints . Patients were followed on treatment for two years . Data from 6,602 patients were analysed . Factorial analysis demonstrated a highly significant effect for ASA and for dipyridamole in reducing the risk of stroke ( p < or = 0.001 ) and stroke or death combined ( p < 0.01 ) . In pairwise comparisons , stroke risk in comparison to placebo was reduced by 18 % with ASA alone ( p = 0.013 ) ; 16 % with dipyridamole alone ( p = 0.039 ) ; and 37 % with combination therapy ( p < 0.001 ) . Risk of stroke or death was reduced by 13 % with ASA alone ( p = 0.016 ) ; 15 % with dipyridamole alone ( p = 0.015 ) ; and 24 % with the combination ( p < 0.001 ) . The treatment had no statistically significant effect on the death rate alone . Factorial analysis also demonstrated a highly significant effect of ASA ( p < 0.001 ) and dipyridamole ( p < 0.01 ) for preventing TIA . The risk reduction for the combination was 36 % ( p < 0.001 ) in comparison with placebo .  Headache was the most common adverse event , occurring more frequently in dipyridamole-treated patients . All-site bleeding and gastrointestinal bleeding were significantly more common in patients who received ASA in comparison to placebo or dipyridamole . We conclude that ( 1 ) ASA 25 mg twice daily and dipyridamole , in a modified-release form , at a dose of 200 mg twice daily have each been shown to be equally effective for the secondary prevention of ischemic stroke and TIA ; ( 2 ) when co-prescribed the protective effects are additive , the combination being significantly more effective than either agent prescribed singly ; ( 3 ) low-dose ASA does not eliminate the propensity for induced bleeding From 1979 - 85 , 2435 patients with a transient ischaemic attack or minor ischaemic stroke were r and omly allocated to receive long term " blind " treatment with aspirin 600 mg twice daily ( n = 815 ) , aspirin 300 mg once daily ( n = 806 ) or placebo ( n = 814 ) . No patient was lost to follow up . The " intention to treat " comparison included all the serious vascular events and deaths which occurred before the end of the follow up period on 30 September 1986 . There was no difference in efficacy between the 300 mg and 1200 mg daily doses of aspirin , but the lower dose was undoubtedly less gastrotoxic . Also , there was no definite difference in the response of  males and females to aspirin . The odds of suffering a major stroke , myocardial infa rct ion or vascular death were 15 % less in the combined aspirin groups compared with the placebo group ( 95 % confidence interval 29 % reduction to 3 % increase in odds ) which is compatible with the continuing overview of all the similar trials of antiplatelet drugs where the relative reduction in odds was 25 % . There was no statistically significant reduction in the likelihood of either disabling major stroke and vascular death or vascular death occurring The effects of dipyridamole in association with acetylsalicylic acid were compared with the effects of acetylsalicylic acid alone in patients with peripheral vascular disease . The following parameters were studied in each patient : symptoms-free interval on the treadmill , ankle-arm arterial pressure gradient , oscillographic index , venous occlusion plethysmography and any untoward reactions . Changes were observed in the pain-free interval ( p less than 0.005 ) , and in the venous occlusion plethysmography ( p less than 0.001 ) in the patients treated with the two drugs in association Since Heberden 's classic description of angina pectoris in 1768 , a satisfactory treatment has been sought . Nitroglycerin , which is the st and ard treatment , may have unpleasant side effects due to vasodilatation , and its duration of action is relatively short . From the rapid turnover of a multitude of alleged long-acting coronary vasodilators marketed , it is apparent that an ideal compound which is both effective and devoid of side effects has not been found . Fischer and Roch reported in 1951 the synthesis of a new group of compounds with two pyrimidine rings . One of these compounds , dipyridamole ( Persantine ) , was subsequently shown to produce a significant increase in coronary blood flow 1 and an increase in intercoronary anastomoses in dogs with surgically induced coronary artery constriction . 2 In patients with angina pectoris , several uncontrolled , or only partially double-blind , studies have indicated that dipyridamole produced subjective improvement . 3 - 6 In contrast , four double-blind studies 7 - 10 have BACKGROUND Oral dipyridamole induces accumulation of endogenous adenosine , which in a hypoxic milieu exerts experimentally an angiogenic effect on coronary collateral circulation . A meta- analysis of 13 r and omized placebo-controlled trials published between 1960 and 1992 showed evidence of benefit for dipyridamole in the treatment of angina pectoris , especially with longer duration of treatment . Aim To assess the efficacy and safety of dipyridamole in the treatment of patients with chronic stable angina in a large scale , international , r and omized , placebo-controlled , parallel group study . METHODS Four hundred patients with chronic stable angina pectoris and a positive treadmill exercise test were r and omized to receive either modified release dipyridamole ( 200 mg b.i.d . p.o . , n=198 ) or corresponding placebo ( n=202 ) , for 24 weeks as an add-on to conventional antianginal therapy and for 4 additional weeks as monotherapy -- the latter after withdrawal of st and ard treatment with calcium antagonists and /or beta-blockers 
    Output:
    