Aspirin plus dipyridamole versus aspirin alone after cerebral ischaemia of arterial origin (ESPRIT): randomised controlled trial. Secondary stroke prevention with low-dose aspirin, sustained release dipyridamole alone and in combination. ESPS Investigators. European Stroke Prevention Study. Prevention of serious vascular events by aspirin amongst patients with peripheral arterial disease: randomized, double-blind trial. A Randomised Controlled Trial of Triple Antiplatelet Therapy (Aspirin, Clopidogrel and Dipyridamole) in the Secondary Prevention of Stroke: Safety, Tolerability and Feasibility Low‐dose acetylsalicylic acid (ASA) plus dipyridamole versus dipyridamole alone in the prevention of stroke in patients with reversible ischemic attacks "AICLA" controlled trial of aspirin and dipyridamole in the secondary prevention of athero-thrombotic cerebral ischemia. A randomized trial of anticoagulants versus aspirin after cerebral ischemia of presumed arterial origin Comparison between aspirin combined with dipyridamole versus aspirin alone within 48 hours after ischemic stroke event for prevention of recurrent stroke and improvement of neurological function: a preliminary study. Aspirin and extended-release dipyridamole versus clopidogrel for recurrent stroke. Recurrent Ischemic Lesions After Acute Atherothrombotic Stroke: Clopidogrel Plus Aspirin Versus Aspirin Alone Effect of Combined Aspirin and Extended-Release Dipyridamole Versus Clopidogrel on Functional Outcome and Recurrence in Acute, Mild Ischemic Stroke: PRoFESS Subgroup Analysis Early treatment with aspirin plus extended-release dipyridamole for transient ischaemic attack or ischaemic stroke within 24 h of symptom onset (EARLY trial): a randomised, open-label, blinded-endpoint trial The prevention of progression of arterial disease and diabetes (POPADAD) trial: factorial randomised placebo controlled trial of aspirin and antioxidants in patients with diabetes and asymptomatic peripheral arterial disease European Stroke Prevention Study 2. Dipyridamole and acetylsalicylic acid in the secondary prevention of stroke Aspirin for Stroke Prevention in Elderly Patients With Vascular Risk Factors: Japanese Primary Prevention Project Effect of dipyridamole plus aspirin on hemodialysis graft patency. Aspirin for prevention of cardiovascular events in a general population screened for a low ankle brachial index: a randomized controlled trial.
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 Patients who had survived a stroke or transient ischaemic attacks ( TIA ) were admitted to a trial of low-dose aspirin ( 50 mg ) alone , sustained release dipyridamole ( 400 mg/day ) alone , or a combination of the two agents , and results compared with a placebo over 24 months . This low-dose aspirin regimen produced in pairwise comparisons a significant risk reduction of 18 % for stroke , 13 % for stroke and /or death but no reduction in all cause mortality . The sustained release dipyridamole produced a significant risk reduction of 16 % for stroke , 15 % for stroke and /or death but no significant reduction of mortality . In combination , aspirin and dipyridamole produced a risk reduction of 37 % in stroke , 24 % in stroke and /or death , and no reduction in mortality . Similar findings were found in TIA , which was a secondary endpoint . These results are highly significant in comparison with placebo . As expected , there were enhanced reports of alimentary side-effects in the aspirin groups and also enhanced bleeding .  Dipyridamole was associated with a slight increase in headache , which resolved in most patients if therapy was continued . The conclusions are that 50 mg/day of aspirin alone or 400 mg/day of sustained release dipyridamole alone are equally effective in stroke and TIA prevention . When used in combination the effects were additive and were significantly more effective than the single agents OBJECTIVE To assess the prophylactic efficacy of aspirin and a high-dose antioxidant vitamin combination in patients with peripheral arterial disease ( PAD ) in terms of reduction of the risk of a first vascular event ( myocardial infa rct ion , stroke , vascular death ) and critical limb ischaemia . DESIGN R and omized , placebo-controlled , double-blind clinical trial with 2 x 2 factorial design . SETTING Thirty-seven European angiology/vascular medicine units . SUBJECTS A total of 366 out patients with stage I-II PAD documented by angiography or ultrasound , with ankle/brachial index < 0.85 or toe index < 0.6 ; 210 patients completed the follow-up . INTERVENTIONS Four treatment groups : ( i ) oral aspirin ( 100 mg daily ) , ( ii ) oral antioxidant vitamins ( 600 mg vitamin E , 250 mg vitamin C and 20 mg beta-carotene daily ) , ( iii ) both or ( iv ) neither , given for 2 years . MAIN OUTCOME MEASURE Major vascular events ( cardiovascular death , myocardial infa rct ion or stroke ) and critical leg ischaemia . RESULTS Seven of 185 patients allocated aspirin and 20 of 181 allocated placebo suffered a major vascular event ( risk reduction 64 % , P = 0.022 ) ; five and eight patients , respectively , suffered critical leg ischaemia ( total 12 vs. 28 , P = 0.014 ) . There was no evidence that antioxidant vitamins were beneficial ( 16/185 vs. 11/181 vascular events ) . Neither treatment was associated with any significant increase in adverse events . Inclusion of this trial in a meta- analysis of other r and omized trials of anti-platelet therapy in PAD makes the overall results highly significant ( P < 0.001 ) and suggests that low-dose aspirin reduces the incidence of vascular events by 26 % . CONCLUSIONS For the first time direct evidence shows that low-dose aspirin should routinely be considered for PAD patients , including those with concomitant type 2 diabetes Background Aspirin , dipyridamole and clopidogrel are effective in secondary vascular prevention . Combination therapy with three antiplatelet agents might maximise the benefit of antiplatelet treatment  in the secondary prevention of ischaemic stroke . Methodology /Principal Findings A r and omised , parallel group , observer-blinded phase II trial compared the combination of aspirin , clopidogrel and dipyridamole with aspirin alone .  Adult patients with ischaemic stroke or transient ischaemic attack ( TIA ) within 5 years were included . The primary outcome was tolerability to treatment assessed as the number of patients completing r and omised treatment . Recruitment was halted prematurely after publication of the ESPRIT trial ( which confirmed that combined aspirin and dipyridamole is more effective than aspirin alone ) . 17 patients were enrolled : male 12 ( 71 % ) , mean age 62 ( SD 13 ) years , lacunar stroke syndrome 12 ( 71 % ) , median stroke/TIA onset to r and omisation 8 months . Treatment was discontinued in 4 of 9 ( 44 % ) patients receiving triple therapy vs. none of 8 taking aspirin ( p = 0.08 ) . One recurrent stroke occurred in a patient in the triple group who was noncompliant of all antiplatelet medications . The number of patients with adverse events and bleeding complications , and their severity , were significantly greater in the triple therapy group ( p<0.01 ) . Conclusions / Significance Long term triple antiplatelet therapy was asociated with a significant increase in adverse events and bleeding rates , and their severity , and a trend to increased discontinuations . However , the patients had a low risk of recurrence and future trials should focus on short term therapy in high risk patients characterised by a very recent event or failure of dual antiplatelet therapy . Trial Registration Controlled-Trials.com IS RCT Abstract A total of 243 patients who had reversible ischemic attacks ( RIA ) were su bmi tted to clinical trial to determine whether dipyridamole ( 400 mg/day ) ( D ) or aspirin ( 100 mg/48 hours ) + dipyridamole ( 300 mg/day ) ( ASA+D ) would produce significant reduction in the subsequent occurrence of RIA and completed stroke .  One hundred and fifteen were selected for Group ASA+D and 71 were treated with dipyridamole only . The treatment groups were similar in relation to age , sex , risk factors , duration and presumed vascular territory of RIA , incidence of alterations of arterial supra‐aortic trunks , cerebral infa rct ( CT scan ) , and platelet function . Patients were followed for a mean time of 21 months 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 Aspirin is only modestly effective in the secondary prevention after cerebral ischemia . Studies in other vascular disorders suggest that anticoagulant drugs in patients with cerebral ischemia of presumed arterial ( noncardiac ) origin might be more effective . The aim of the Stroke Prevention in Reversible Ischemia Trial ( SPIRIT ) therefore was to compare the efficacy and safety of 30 mg aspirin daily and oral anticoagulation ( international normalized ratio [ INR ] 3.0–4.5 ) . Patients referred to a neurologist in one of 58 collaborating centers because of a transient ischemic attack or minor ischemic stroke ( Rankin grade $ 3 ) were eligible . R and omization was concealed , treatment assignment was open , and assessment of outcome events was masked . The primary measure of outcome was the composite event “ death from all vascular causes , nonfatal stroke , nonfatal myocardial infa rct ion , or nonfatal major bleeding complication . ” The trial was stopped at the first interim analysis . A total of 1,316 patients participated ; their mean follow‐up was 14 months . There was an excess of the primary outcome event in the anticoagulated group ( 81 of 651 ) versus 36 of 665 in the aspirin group ( hazard ratio , 2.3 ; 95 % confidence interval [ CI ] , 1.6–3.5 ) . This excess could be attributed to 53 major bleeding complications ( 27 intracranial ; 17 fatal ) during anticoagulant therapy versus 6 on aspirin ( 3 intracranial ; 1 fatal ) . The bleeding incidence increased by a factor of 1.43 ( 95 % CI , 0.96–2.13 ) for each 0.5 unit increase of the achieved INR . Anticoagulant therapy with an INR range of 3.0 to 4.5 in patients after cerebral ischemia of presumed arterial origin is not safe . The efficacy of a lower intensity anticoagulation regimen remains to be determined OBJECTIVES To determine efficacy and tolerability of aspirin plus dipyridamole ( combination ) versus aspirin alone in acute intervention treatment after acute ischemic stoke among Thai patients . MATERIAL AND METHOD This pilot study enrolled ischemic stroke patients within 48 hours and r and omized to aspirin 300 mg/d or combination ( aspirin 300 mg/d+ st and ard release dipyridamole 75 mg thrice a day ) and followed up for 6 months . Endpoints were recurrent ischemic stroke , transient ischemic attack and vascular death . Side effects were recorded . National Institutes of Health Stroke Scale was assessed at entry and at 6 months period for determining neurological functions . RESULTS Of 38 patients , mean age was 64.3 years . Male and female were 52.6 % and 47.4 % respectively . There were 18 patients in the aspirin group and 20 patients in the combination group . No patient developed end point events or no significant adverse event in both groups . The combination group showed more improvement in neurological function than the aspirin group ( p-value 0.009 ) . CONCLUSION This pilot study showed equal efficacy and tolerability of the combination group and aspirin alone in acute intervention treatment for prevention of recurrent stroke or vascular death within 6 months BACKGROUND Recurrent stroke is a frequent , disabling event after ischemic stroke . This study compared the efficacy and safety of two antiplatelet regimens -- aspirin plus extended-release dipyridamole ( ASA-ERDP ) versus clopidogrel . METHODS In this double-blind , 2-by-2 factorial trial , we r and omly assigned patients to receive 25 mg of aspirin plus 200 mg of extended-release dipyridamole twice daily or to receive 75 mg of clopidogrel daily . The primary outcome was first recurrence of stroke . The secondary outcome was a composite of stroke , myocardial infa rct ion , or death from vascular causes . Sequential statistical testing of noninferiority ( margin of 1.075 ) , followed by superiority testing , was planned . RESULTS A total of 20,332 patients were followed for a mean of 2.5 years .  Recurrent stroke occurred in 916 patients ( 9.0 % ) receiving ASA-ERDP and in 898 patients ( 8.8 % ) receiving clopidogrel ( hazard ratio , 1.01 ; 95 % confidence interval [ CI ] , 0.92 to 1.11 ) . The secondary outcome occurred in 1333 patients ( 13.1 % ) in each group ( hazard ratio for ASA-ERDP , 0.99 ; 95 % CI , 0.92 to 1.07 ) . There were more major hemorrhagic events among ASA-ERDP recipients ( 419 [ 4.1 % ] ) than among clopidogrel recipients ( 365 [ 3.6 % ] ) ( hazard ratio , 1.15 ; 95 % CI , 1.00 to 1.32 ) , including intracranial hemorrhage ( hazard ratio , 1.42 ; 95 % CI , 1.11 to 1.83 ) . The net risk of recurrent stroke or major hemorrhagic event was similar in the two groups ( 1194 ASA-ERDP recipients [ 11.7 % ] , vs. 1156 clopidogrel recipients [ 11.4 % ] ; hazard ratio , 1.03 ; 95 % CI , 0.95 to 1.11 ) . CONCLUSIONS The trial did not meet the predefined criteria for noninferiority but showed similar rates of recurrent stroke with ASA-ERDP and with clopidogrel . There is no evidence that either of the two treatments was superior to the other in the prevention of recurrent stroke . ( Clinical Trials.gov number , NCT00153062 . Background and Purpose — In patients with acute ischemic stroke caused by large artery atherosclerosis , clopidogrel plus aspirin versus aspirin alone might be more effective to prevent recurrent cerebral ischemia . However , there is no clear evidence . Methods — In this multicenter , double-blind , placebo-controlled trial , we r and omized 358 patients with acute ischemic stroke of presumed large artery atherosclerosis origin within 48 hours of onset to clopidogrel ( 75 mg/d without loading dose ) plus aspirin ( 300-mg loading followed by 100 mg/d ) or to aspirin alone ( 300-mg loading followed by 100 mg/d ) for 30 days . The primary outcome was new symptomatic or asymptomatic ischemic lesion on magnetic resonance imaging within 30 days . Secondary outcomes were 30-day functional disability , clinical stroke recurrence , and composite of major vascular events . Safety outcome was any bleeding . Results — Of 358 patients enrolled , 334 ( 167 in each group ) completed follow-up magnetic resonance imaging . The 30-day new ischemic lesion recurrence rate was comparable between the clopidogrel plus aspirin and the aspirin monotherapy groups ( 36.5 % versus 35.9 % ; relative risk , 1.02 ; 95 % confidence interval , 0.77–1.35 ; P=0.91 ) . Of the recurrent ischemic lesions , 94.2 % were clinical ly asymptomatic . There were no differences in secondary outcomes between the 2 groups . Any bleeding were more frequent in the combination group than in the aspirin monotherapy group , but the difference was not significant ( 16.7 % versus 10.7 % ; P=0.11 ) . One hemorrhagic stroke occurred in the clopidogrel plus aspirin group . Conclusions — Clopidogrel plus aspirin might not be superior to aspirin alone for preventing new ischemic lesion and clinical vascular events in patients with acute ischemic stroke caused by large artery atherosclerosis . Clinical Trial Registration — URL : http://www . clinical trials.gov . Unique identifier : NCT00814268 Background and Purpose — Long-term antiplatelet therapy is effective at reducing recurrence after ischemic stroke . However , the relative safety and efficacy of combined aspirin-dipyridamole or clopidogrel are not known in patients with acute ischemic stroke . Methods — The factorial PRoFESS secondary prevention trial assessed antiplatelet and blood pressure – lowering strategies in 20 332 patients , 1360 of whom were r and omized within 72 hours of ischemic stroke to combined aspirin ( Asp ; 25 mg BID ) and extended-release dipyridamole ( ER-DP ; 200 mg BID , n=672 )  or clopidogrel ( 75 mg/d , n=688 ) . The primary outcome for this post hoc subgroup analysis was functional outcome at 30 days ; secondary outcomes included recurrence and death by 90 days . Analyses were adjusted for baseline prognostic variables and blood pressure treatment assignment . Results — Patients were representative of the whole trial ( age 67 years , National Institutes of Health Stroke Scale score 3 , small-artery occlusion 59 % ) , and baseline variables were similar between treatment groups . The mean time from stroke to recruitment was 58 hours . By 90 days , treatment was no longer being taken in 121 ( 18 % ) patients r and omized to Asp/ER-DP and in 86 ( 12.5 % ) assigned to clopidogrel ( P=0.006 ) . Combined death or dependency ( shift analysis of modified Rankin Scale score at day 30 ) did not differ between treatment groups ( odds ratio [OR]=0.97 ; 95 % CI , 0.79 to 1.19 ) . Nonsignificant trends to reduced recurrence ( OR=0.56 ; 95 % CI , 0.26 to 1.18 ) and vascular events ( OR=0.71 ; 95 % CI , 0.36 to 1.37 ) were present with Asp/ER-DP . Rates of death , major bleeding , and serious adverse events did not differ between treatment groups . Conclusions — Treatment with combined Asp/ER-DP vs clopidogrel in 1360 patients with acute , mild ischemic stroke did not differ in terms of effects on functional outcome , recurrence , death , bleeding , or serious adverse events . Both treatments were practical to administer BACKGROUND Little is known about the best antiplatelet treatment immediately after ischaemic stroke or transient ischaemic attack ( TIA ) . The EARLY trial aim ed to compare outcome in patients given aspirin plus extended-release dipyridamole twice daily either within 24 h of stroke or TIA or after 7 days of aspirin monotherapy . METHODS In 46 stroke units in Germany , patients aged 18 years or more who presented with symptoms of an acute ischaemic stroke that caused a measurable neurological deficit ( National Institutes of Health stroke scale score < or = 20 ) were r and omly assigned to receive 25 mg aspirin plus 200 mg extended-release dipyridamole open-label twice daily or 100 mg aspirin monotherapy open-label once daily for 7 days . Patients were r and omised by use of a pseudor and om number generator . All patients were then given open-label aspirin plus extended-release dipyridamole for up to 90 days . The primary endpoint was modified Rankin scale score as recorded by central ised , blinded assessment by telephone ( tele-mRS ) at 90 days . Vascular adverse events ( non-fatal stroke , TIA , non-fatal myocardial infa rct ion , and major bleeding complications ) and mortality were assessed in a composite safety and efficacy endpoint . Patients were analysed as treated . This trial is registered , number NCT00562588 . FINDINGS Between July , 2007 , and February , 2009 , 543 patients were treated : 283 received early aspirin plus extended-release dipyridamole and 260 received aspirin plus extended-release dipyridamole after 7 days on aspirin . At day 90 , 154 ( 56 % ) patients in the aspirin plus early extended-release dipyridamole group and 133 ( 52 % ) in the aspirin plus later extended-release dipyridamole group had no or mild disability ( tele-mRS 0 or 1 ; difference 4.1 % , 95 % CI -4.5 to 12.6 , p=0.45 ) . 28 patients in the early initiation group and 38 in the late initiation group reached the composite endpoint ( hazard ratio 0.73 , 95 % CI 0.44 - 1.19 p=0.20 ) . INTERPRETATION Early initiation of aspirin plus extended-release dipyridamole within 24 h of stroke onset is likely to be as safe and effective in preventing disability as is later initiation after 7 days . FUNDING Boehringer Ingelheim 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 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 Background and Purpose — The effect of aspirin in primary prevention of stroke is controversial among clinical trials conducted in Western countries , and no data are available for Asian population s with a high risk of intracranial hemorrhage . The objective of this study was to evaluate the effect of aspirin on the risk of stroke and intracranial hemorrhage in the Japanese Primary Prevention Project ( JPPP ) . Methods — A total of 14 464 patients ( age , 60–85 years ) with hypertension , dyslipidemia , and diabetes mellitus participated and were r and omized into 2 treatment groups : 100 mg of aspirin or no aspirin . The median follow-up period was 5.02 years . Results — The cumulative rate of fatal or nonfatal stroke was similar for the aspirin ( 2.068 % ; 95 % confidence interval [ CI ] , 1.750–2.443 ) and no aspirin ( 2.299 % ; 95 % CI , 1.963–2.692 ) groups at 5 years ; the estimated hazard ratio was 0.927 ( 95 % CI , 0.741–1.160 ; P=0.509 ) . Aspirin nonsignificantly reduced the risk of ischemic stroke or transient ischemic attack ( hazard ratio , 0.783 ; 95 % CI , 0.606–1.012 ; P=0.061 ) and nonsignificantly increased the risk of intracranial hemorrhage ( hazard ratio , 1.463 ; 95 % CI ; 0.956–2.237 ; P=0.078 ) . A Cox regression adjusted by the risk factors for all stroke , which were age > 70 years , smoking , and diabetes mellitus , supported the above result . Conclusions — Aspirin did not show any net benefit for the primary prevention of stroke in elderly Japanese patients with risk factors for stroke , whereas age > 70 years , smoking , and diabetes mellitus were risk factors for stroke regardless of aspirin treatment . Clinical Trial Registration — URL : http://www . clinical trials.gov . Unique identifier : NCT00225849 BACKGROUND Arteriovenous graft stenosis leading to thrombosis is a major cause of complications in patients undergoing hemodialysis . Procedural interventions may restore patency but are costly . Although there is no proven pharmacologic therapy , dipyridamole may be promising because of its known vascular antiproliferative activity . METHODS We conducted a r and omized , double-blind , placebo-controlled trial of extended-release dipyridamole , at a dose of 200 mg , and aspirin , at a dose of 25 mg , given twice daily after the placement of a new arteriovenous graft until the primary outcome , loss of primary unassisted patency ( i.e. , patency without thrombosis or requirement for intervention ) , was reached . Secondary outcomes were cumulative graft failure and death . Primary and secondary outcomes were analyzed with the use of a Cox proportional-hazards regression with adjustment for prespecified covariates . RESULTS At 13 centers in the United States , 649 patients were r and omly assigned to receive dipyridamole plus aspirin ( 321 patients ) or placebo ( 328 patients ) over a period of 4.5 years , with 6 additional months of follow-up . The incidence of primary unassisted patency at 1 year was 23 % ( 95 % confidence interval [ CI ] , 18 to 28 ) in the placebo group and 28 % ( 95 % CI , 23 to 34 ) in the dipyridamole-aspirin group , an absolute difference of 5 percentage points . Treatment with dipyridamole plus aspirin significantly prolonged the duration of primary unassisted patency ( hazard ratio , 0.82 ; 95 % CI , 0.68 to 0.98 ; P=0.03 ) and inhibited stenosis . The incidences of cumulative graft failure , death , the composite of graft failure or death , and serious adverse events ( including bleeding ) did not differ significantly between study groups . CONCLUSIONS Treatment with dipyridamole plus aspirin had a significant but modest effect in reducing the risk of stenosis and improving the duration of primary unassisted patency of newly created grafts . ( Clinical Trials.gov number , NCT00067119 . 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 stroke or revascularization . Two secondary end points were ( 1 ) all initial vascular events defined as a composite of a primary end point event or angina , intermittent claudication , or transient ischemic attack ; and ( 2 ) all-cause mortality . RESULTS After a mean ( SD ) follow-up of 8.2 ( 1.6 ) years , 357 participants had a primary end point event ( 13.5 per 1000 person-years , 95 % confidence interval [ CI ] , 12.2 - 15.0 ) . No statistically significant difference was found between groups ( 13.7 events per 1000 person-years in the aspirin group vs 13.3 in the placebo group ; hazard ratio [ HR ] , 1.03 ; 95 % CI , 0.84 - 1.27 ) . A vascular event comprising the secondary end point occurred in 578 participants ( 22.8 per 1000 person-years ; 95 % CI , 21.0 - 24.8 ) and no statistically significant difference between groups ( 22.8 events per 1000 person-years in the aspirin group vs 22.9 in the placebo group ; HR , 1.00 ; 95 % CI , 0.85 - 1.17 ) . There was no significant difference in all-cause mortality between groups ( 176 vs 186 deaths , respectively ; HR , 0.95 ; 95 % CI , 0.77 - 1.16 ) . An initial event of major hemorrhage requiring admission to hospital occurred in 34 participants ( 2.5 per 1000 person-years ) in the aspirin group and 20 ( 1.5 per 1000 person-years ) in the placebo group ( HR , 1.71 ; 95 % CI , 0.99 - 2.97 ) . CONCLUSION Among participants without clinical cardiovascular disease , identified with a low ABI based on screening a general population , the administration of aspirin compared with placebo did not result in a significant reduction in vascular events . TRIAL REGISTRATION is rct n.org Identifier : IS RCT N66587262
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
BACKGROUND Patients with limited cerebral ischaemia of arterial origin are at risk of serious vascular events ( 4 % to 11 % annually ) .
Aspirin reduces that risk by 13 % .
In one trial , adding dipyridamole to aspirin was associated with a 22 % risk reduction compared with aspirin alone .
OBJECTIVES To assess the efficacy and safety of dipyridamole versus control in the secondary prevention of vascular events in patients with vascular disease .