title: Persantine Aspirin Trial in cerebral ischemia. The American-Canadian Co-operative Study Group. "AICLA" controlled trial of aspirin and dipyridamole in the secondary prevention of athero-thrombotic cerebral ischemia. Veterans Administration Cooperative Study on Antiplatelet Agents in Diabetic Patients After Amputation for Gangrene: II. Effects of Aspirin and Dipyridamole on Atherosclerotic Vascular Disease Rates Aspirin plus dipyridamole versus aspirin alone after cerebral ischaemia of arterial origin (ESPRIT): randomised controlled trial. European Stroke Prevention Study 2. Dipyridamole and acetylsalicylic acid in the secondary prevention of stroke The United Kingdom transient ischaemic attack (UK-TIA) aspirin trial: final results. Treatment of claudication with dipyridamole and aspirin. Dipyridamole in the treatment of angina pectoris. A double-blind evaluation. Dipyridamole in chronic stable angina pectoris; a randomized, double blind, placebo-controlled, parallel group study. Persantine and aspirin in coronary heart disease. The Persantine-Aspirin Reinfarction Study Research Group. European Stroke Prevention Study. ESPS Group. Aspirin at any dose above 30 mg offers only modest protection after cerebral ischaemia. A comparison of two doses of aspirin (30 mg vs. 283 mg a day) in patients after a transient ischemic attack or minor ischemic stroke. [Treatment of unstable angina with dipyridamole combined with low doses of aspirin. A multicenter pilot double-blind controlled study]. DRUG-INDUCED INHIBITION OF PLATELET FUNCTION DELAYS PROGRESSION OF PERIPHERAL OCCLUSIVE ARTERIAL DISEASE: A Prospective Double-Blind Arteriographically Controlled Trial Anti-platelet therapy in graft thrombosis: results of a prospective, randomized, double-blind study. Persantine-Aspirin Reinfarction Study. Part II. Secondary coronary prevention with persantine and aspirin. Treatment of angina pectoris with dipyridamole: a double-blind study. Dipyridamole: a Controlled Trial of its Effect in Acute Myocardial Infarction Treatment of angina pectoris with dipyridamole: a long-term double blind study. Frequent reocclusion of patent infarct-related arteries between 4 weeks and 1 year: effects of antiplatelet therapy. Controlled Trial of Dipyridamole in Cerebral Vascular Disease
abstract: 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 and /or long-acting ( prophylactic ) nitrates . RESULTS Of the 198 patients r and omized to  dipyridamole  , 134 completed the add-on and only 12 the monotherapy phase . Of the 202 patients r and omized to placebo , 162 reached the add-on and only 12 the monotherapy phase . Serious adverse events occurred in 15 patients with dipyridamole and in 12 with placebo ( 7.6 % vs 6.0 , P=0.52 ) . Increase over the baseline treadmill exercise test was similar in the treatment groups at each stage of the trial for all the main efficacy parameters : total treadmill exercise test duration ; time to first anginal pain ( except for a -13 s difference in favour of placebo at week 24;P=0.040 ) ; time to ST segment depression > 0.1 mVolt ( except for a + 21 s difference in favour of dipyridamole at week 8;P=0.024 ; this latter difference was totally attributable to patients with lower exercise tolerance -- Bruce stage II at study entry ) . CONCLUSION In patients with chronic stable angina treated with regular antianginal background medication , the use of oral dipyridamole is safe and well tolerated . Antianginal and antiischaemic efficacy , as assessed by exercise testing , is comparable to placebo , except for a beneficial effect on time to ischaemia after 2 months , totally attributable to patients with lower exercise tolerance at study entry In the Persantine-Aspirin Reinfa rct ion Study ( PARIS ) trial , 2026 persons who had recovered from myocardial infa rct ion ( MI ) were r and omized into three groups : Persantine plus aspirin ( PR/A ) ( n = 810 ) ; aspirin alone ( ASA ) ( n = 810 ) ; placebo ( PLBO ) ( n = 406 ) . The average length of follow-up study was 41 months . Results for the three specified primary end points were : total mortality 16 % lower in PR/A and 18 % lower in ASA compared with PLBO ; coronary mortality 24 % and 21 % lower ; incidence of nonfatal MI plus fatal coronary disease 25 % and 24 % lower . These differences were not satistically significant by the study criterion ( Z greater than or equal to 2.6 ) . By life-table analysis , the rates of coronary mortality and coronary incidence were about 50 % lower in the PR/A group than in the PLBO group from 8 - 24 months , and for coronary incidence all Z values were greater than or equal to 2.6 ; ASA rates were about 30 % lower than PLBO rates , and for coronary incidence , Z values were greater than or equal to 2.6 at two points . For these end points , from 8 - 20 months , PR/A rates were about 30 % lower than ASA rates , but all Z values were less than 2.0 PR/A and ASA patients entering within 6 months of last MI showed the largest percentage reductions in mortality ; only the difference between PR/A and PLBO groups for 3-year coronary mortality yielded a Z value of 2.6 We compared the outcomes of 2,500 patients who suffered from previous cerebrovascular disorders ( transient ischemic attacks , reversible ischemic neurologic deficits , or completed strokes ) treated with acetylsalicylic acid plus dipyridamole or matched placebo and followed for 2 years . Treatment was associated with a 33.5 % reduction ( p less than 0.001 ) in the incidence of all end points ( deaths from all causes or strokes ) by intention-to-treat analysis and a 36.5 % reduction ( p less than 0.001 ) by explanatory analysis . End point reduction appeared to be similar in men and women . The effect of treatment was similar regardless of the patients ' age , nature of the qualifying cerebrovascular event , site of the responsible lesion , and diastolic blood pressure . Our results demonstrate the efficacy of combined therapy , but the efficacy of  acetylsalicylic acid or dipyridamole alone and the most effective acetylsalicylic acid dosage remain in question There is continuing debate about the relative efficacy of low ( < 100 mg per day ) , medium ( 300 to 325 mg per day ) , and high ( > 900 mg per day ) doses of aspirin in patients after a transient ischaemic attack or non-disabling stroke . The purpose of this study was to resolve the issue . Thus a minimeta- analysis was performed on data from 10 r and omised trials of aspirin only v control treatment in 6171 patients after a transient ischaemic attack or nondisabling stroke . The data on the trials were listed in an appendix of the report on the second cycle of the Antiplatelet Trialists ' Collaboration . There was virtually no difference in relative risk reduction for low , medium , and high doses of aspirin ( 13 % , 9 % , and 14 % respectively ) . This equivalence corresponds with the results of the UK-TIA trial in a direct comparison of 300 and 1200 mg . The Dutch TIA trial showed no difference in efficacy of 30 and 283 mg . It is concluded that aspirin at any dose above 30 mg daily prevents 13 % ( 95 % confidence interval 4 - 21 ) of vascular events and that there is a need for more efficacious drugs BACKGROUND Aspirin is known to improve the outcome of patients who have had a cerebral transient ischemic attack , but the optimal dose of aspirin remains uncertain . Experimental evidence indicates that 30 mg of aspirin daily alters platelet aggregation more favorably than the 300-mg dose currently used in patients after transient ischemic attack or minor ischemic stroke . METHODS We assessed the effects of two doses of a water-soluble preparation of acetylsalicylic acid , or aspirin ( 30 mg vs. 283 mg a day ) , on the occurrence of death from all vascular causes , nonfatal stroke , or nonfatal myocardial infa rct ion in a double-blind , r and omized , controlled clinical trial in patients who had had a transient ischemic attack or minor stroke . A total of 3131 patients participated in the study . The mean follow-up was 2.6 years . RESULTS In the group assigned to receive 30 mg of aspirin , the frequency of death from vascular causes , nonfatal stroke , or nonfatal myocardial infa rct ion was 228 of 1555 ( 14.7 percent ) , as compared with 240 of 1576 ( 15.2 percent ) in the group assigned to receive 283 mg . The age- and sex-adjusted hazard ratio for the group receiving the lower dose was 0.91 ( 95 percent confidence interval , 0.76 to 1.09 ) . There were slightly fewer major bleeding complications in the 30-mg group than in the 283-mg group ( 40 vs. 53 ) , and significantly fewer reports of minor bleeding ( 49 vs. 84 ) . Fewer patients receiving 30 mg of aspirin reported gastrointestinal symptoms ( 164 vs. 179 ) and other adverse effects ( 73 vs. 90 ) . CONCLUSIONS Our data indicate that 30 mg of aspirin daily is no less effective in the prevention of vascular events than a 283-mg dose in patients with a transient ischemic attack or minor stroke , and has fewer adverse effects In order to assess the usefulness of a combination of low-dose aspirin ( 25 mg b.i.d . ) with dipyridamole ( 200 mg b.i.d . ) in the prevention of major coronary events in patients with acute unstable angina , we performed a prospect i ve , double-blind , placebo-controlled study involving 88 consecutive patients admitted to three Hospital Departments of Cardiology . The patients entered the study as soon as possible after hospital admission , and were treated and followed up to one year . There was no appreciable difference in side effects and adverse reactions between the treatment and control group . The incidence of cardiac death and /or nonfatal myocardial infa rct ion during the whole period of observation was 14 % ( 6/44 ) in the treatment group and 25 % ( 11/44 ) in the placebo group by " intention-to-treat " analysis ; 16 % ( 4/25 ) and 32 % ( 10/31 ) , respectively , by " drug-efficacy " analysis ( p = 0.21 by Fisher 's exact test , non significant difference ) . However , when considering the only events occurred in the first month ( 2/44 in the treatment group and 9/44 in the placebo group , amounting to 4.5 and 20 percent , respectively ) , the combination of  dipyridamole  with  low-dose aspirin  reached a statistically significant protective effect ( p = 0.04 ) . The results of this pilot study provide strong evidence for a beneficial effect of the regimen tested in patients with acute unstable angina , at least in the first weeks of treatment , while at the same time suggesting a safe alternative for patients with contraindications to higher doses of aspirin 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 Hemodialysis ( HD ) vascular access thrombosis remains a major cause of morbidity , accounting for 17.4 % of all HD patient hospital admissions in 1986 . We initiated this prospect i ve , r and omized , double-blind , placebo-controlled , parallel group study to examine if dipyridamole and /or aspirin decreased the rate of thrombosis of exp and ed polytetrafluoroethylene ( ePTFE ) grafts in HD patients . Two patient groups were studied : Type I -- with a new ePTFE graft ; and Type II -- with thrombectomy and /or revision of a previously placed ePTFE graft . One hundred and seven patients were followed for 18 months or until the first thrombotic episode . Actuarial analysis of Type I patients showed cumulative thrombosis rates ( mean + /- SEM ) of 21 + /- 9 % on dipyridamole alone , compared with 25 + /- 11 % on dipyridamole and aspirin combination , 42 + /- 13 % on placebo , and 80 + /- 12 % on aspirin alone . The relative risk of thrombosis with dipyridamole was 0.35 ( P = 0.02 ) and that for aspirin was 1.99 ( P = 0.18 ) . In Type II patients , the rate of thrombosis was high in all study drug and placebo groups ( overall 78 % thrombosis ) and actuarial analysis was not carried out because of the small number of patients enrolled . We conclude that dipyridamole is beneficial in patients with new ePTFE grafts and that aspirin does not improve the risk of thrombosis in ePTFE grafts . Neither dipyridamole nor aspirin has any beneficial effect in patients with prior thrombosis of ePTFE grafts In the Persantine-Aspirin Reinfa rct ion Study , Part II ( PARIS II ) , 3,128 persons who had recovered from myocardial infa rct ion , suffered from 4 weeks to 4 months previously , were r and omized into two groups : dipyridamole ( Persantine ) plus aspirin ( n = 1,563 ) and placebo ( n = 1,565 ) . The average length of follow-up was 23.4 months . Prespecified primary end points were coronary incidence ( definite nonfatal myocardial infa rct ion plus death due to recent or acute cardiac event ) , coronary mortality ( death due to recent or acute cardiac event ) and total mortality , each at 1 year of patient follow-up and at the end of the study . Coronary incidence in the Persantine plus aspirin group was significantly lower than in the placebo group , both at 1 year ( 30 % reduction ) and at the end of the study ( 24 % reduction ) . The statistically significant differences in coronary incidence , at 1 year and at the end of the study , in favor of the combination treatment remained after adjustment for multiple baseline variables and adjustment for multiple testing ( three end points for two time periods ) . Although there were reductions for other end points , these differences were not statistically significant . Coronary mortality was 20 % lower in the Persantine plus aspirin group compared with the placebo group at 1 year , and 6 % lower overall . Total mortality in the treated group compared with the placebo group was 11 % lower at 1 year and 3 % lower overall . The reduced rates of coronary incidence largely reflected lower rates of definite nonfatal myocardial infa rct ion in the Persantine plus aspirin group . Several subgroups were defined a priori and at the end of the study . The beneficial effect of Persantine plus aspirin compared with placebo for coronary incidence tended to be greater for the following groups of patients : those who had a non-Q wave infa rct ; those who were not taking digitalis ; those who were receiving beta-receptor blocking drugs at baseline ; those who were in New York Heart Association functional class I ; those who had had only one myocardial infa rct ion ; or those who were enrolled in the study early , that is within 85 days of the qualifying myocardial infa rct ion : In a double-blind study , 48 patients ( age range , 47 to 75 ) with angina pectoris received either dipyridamole ( Persantine ) ( 200 mg daily ) or placebo for an average of five months . Nitroglycerin was taken sublingually as required for relief of acute attacks . Previous use of long-acting nitrates had produced no significant improvement . Of the 26 patients receiving dipyridamole , 21 ( 81 per cent ) showed an overall satisfactory clinical response ( marked or moderate improvement ) compared to 2 ( 9 per cent ) of the 22 receiving placebo . The difference between the two treatments was statistically significant . Evaluation of objective criteria also showed the superiority of dipyridamole . The mean improvement for drug group vs. placebo group was as follows : decrease in anginal attacks , 48/24 per cent ; decrease in need for nitroglycerin , 50/18 per cent ; and increase in walking distance , 84/36 per cent . In terms of subjective evaluation of anginal pain , 69 per cent of the drug group improved compared to 18 per cent of the placebo group . Two patients had reactions while taking the drug . Transient blurred vision was noted by one patient , but it did not interfere with continuation of dipyridamole .  Nausea and insomnia in another patient ( not in the final study group ) caused cessation of therapy . No reactions were reported among the placebo patients . From the results of this controlled study it is concluded that dipyridamole , a non-nitrate coronary vasodilator , is a relatively safe and effective agent for the long-term treatment of patients with angina pectoris A controlled trial of oral dipyridamole in 103 patients with acute myocardial infa rct ion showed no difference in the number of complications or deaths in either the control or the treated groups . It is concluded that dipyridamole has no benefit in acute myocardial infa rct ion Abstract In a double blind study of 7 months ' duration , 56 patients with chronic angina pectoris associated with ischemic heart disease received dipyridamole ( 50 mg tid ) or placebo in carefully r and omized order . Patients were observed for 4 months while on previous medication , usually nitrates , to determine baseline values . They were also followed for 2 months without any long-acting vasodilator drugs after completion of the double blind study . Of 28 patients on dipyridamole  , 22 ( 78.6 per cent ) had a satisfactory ( excellent or good ) clinical response , 1 had a fair response , and 5 responded poorly . In 28 on  placebo  , response was satisfactory in none , fair in 3 , and poor in 25 . Response to the drug was statistically highly significant compared to placebo , P The first signs of improvement occurred after 2 or 3 months of therapy , with maximal improvement at 3 to 6 months . In most of the satisfactory responses , anginal attacks disappeared completely , nitroglycerin was no longer required , and walking distance increased 4–6-fold . Prolonged dipyridamole therapy usually produced a greater beneficial effect than the previous use of long-acting nitrates . No adverse reactions were experienced on the drug or on placebo . This double blind study appears to confirm the results of previous investigations and demonstrates that dipyridamole is an effective , well tolerated agent for long-term treatment of angina pectoris . It is sometimes of benefit in patients unresponsive to other vasodilator drugs OBJECTIVES This study assessed the effect of the combination of aspirin and dipyridamole on patency of the infa rct -related artery between 4 weeks and 1 year after myocardial infa rct ion . BACKGROUND Patency of the infa rct -related artery is an important determinant of prognosis after myocardial infa rct ion . The incidence of late reocclusion and the effects of antiplatelet therapy are unknown . METHODS To investigate the importance of antiplatelet therapy for the prevention of late reocclusion , 215 patients who had a patent infa rct -related artery 4 weeks after myocardial infa rct ion were r and omized in a double-blind manner to receive either a combination of 25 mg of aspirin and 200 mg of dipyridamole twice daily or placebo . One hundred fifty-four patients underwent further coronary arteriography 1 year later . RESULTS At 1 year , 38 ( 25 % ) of 154 patients had reocclusion of the infa rct -related artery ; 18 ( 23 % ) of 79 patients receiving aspirin and dipyridamole had late reocclusion versus 20 ( 27 % ) of 75 who received placebo ( p = NS ) . The rate of reocclusion was related to the severity of the residual coronary artery stenosis at 4 weeks ( < 50 % stenosis 9.2 % ; 50 % to 69 % stenosis 11.6 % ; 70 % to 89 % stenosis 30.4 % ; > or = 90 % stenosis 70 % , p < 0.01 ) . The majority of reocclusions were silent , and only 17 ( 45 % ) of 38 were clinical ly associated with further infa rct ion . There were no differences for a hierarchic end point of cardiac death , myocardial infa rct ion or revascularization ( 14.8 % aspirin and dipyridamole vs. 17.8 % placebo ) . CONCLUSIONS Late reocclusion of the patent infa rct -related artery is a frequent event , occurring in 25 % of patients . Antiplatelet therapy with the combination of aspirin and dipyridamole does not alter the overall rate of late reocclusion . Other strategies are required to reduce late reocclusion A controlled double-blind study of the effect of dipyridamole was performed in 169 patients with established cerebral vascular disease . A dose of 400 mg . was used initially , given daily for an average of 14 months ; the dose was then increased to 800 mg . daily for a further average period of 11 months . When the incidence of cerebral ischaemic episodes during treatment was compared in the drug-treated and placebo-treated groups no significant difference was found
target: 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: 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 .