Aspirin plus dipyridamole versus aspirin alone after cerebral ischaemia of arterial origin (ESPRIT): randomised controlled trial. 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. "AICLA" controlled trial of aspirin and dipyridamole in the secondary prevention of athero-thrombotic cerebral ischemia. Low-molecular weight heparin versus aspirin and dipyridamole after femoropopliteal bypass grafting. Antiplatelet drugs in femoropopliteal vein bypasses: a multicenter trial. Drug-induced inhibition of platelet function delays progression of peripheral occlusive arterial disease. A prospective double-blind arteriographically controlled trial. Effect of dipyridamole plus aspirin on hemodialysis graft patency. Medium intensity oral anticoagulants versus aspirin after cerebral ischaemia of arterial origin (ESPRIT): a randomised controlled trial. A randomized trial of anticoagulants versus aspirin after cerebral ischemia of presumed arterial origin. The Stroke Prevention in Reversible Ischemia Trial (SPIRIT) Study Group. Anti-platelet therapy in graft thrombosis: results of a prospective, randomized, double-blind study. Aprotinin and dipyridamole for the safe reduction of postoperative blood loss. Dipyridamole and postoperative ischemic deficits in aneurysmal subarachnoid hemorrhage. A comparative randomized and placebo-controlled short-term trial of aspirin and dipyridamole for overt type-2 diabetic nephropathy. Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients. [Treatment of unstable angina with dipyridamole combined with low doses of aspirin. A multicenter pilot double-blind controlled study]. Aspirin and extended-release dipyridamole versus clopidogrel for recurrent stroke. Platelet inhibition with ASA/dipyridamole after percutaneous balloon angioplasty in patients with symptomatic lower limb arterial disease. A prospective double-blind trial. Study group on pharmacological treatment after PTA. Controlled trial of aspirin in cerebral ischemia. Part II: surgical group. Low-dose aspirin combined with dipyridamole versus anticoagulants after femoropopliteal percutaneous transluminal angioplasty.
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.
                We did a randomised 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 infarction, 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 Standard Randomised Controlled Trial (number ISRCTN73824458) and with (NCT00161070).
                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 resulted in an overall risk ratio for the composite of vascular death, stroke, or myocardial infarction 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.
                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. We report the results of a randomized 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 infarctions. 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. 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 randomized 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 infarction. Randomization 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 infarctions 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 infarction, 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 infarction. Low-molecular weight heparin has theoretical advantages over aspirin and dipyridamole in maintaining vascular-graft patency by virtue of its better antithrombotic effect and antiproliferative activity on vascular, smooth-muscle cells. We tested the hypothesis that low-molecular weight heparin would be more effective than aspirin and dipyridamole in maintaining graft patency in patients undergoing femoropopliteal bypass grafting. Patients were randomised to receive either a daily injection of 2500 IU low-molecular weight heparin, or 300 mg aspirin with 100 mg dipyridamole 8 hourly for 3 months. 94 patients were randomised to low-molecular weight heparin and 106 to aspirin and dipyridamole. Patients were stratified according to indication for surgery and were followed up for 1 year. Kaplan-Meier estimate of graft patency showed 87% graft survival on low-molecular-weight heparin and 72% on aspirin and dipyridamole at 6 months. At 12 months, the respective figures were 78% and 64%. Stratified survival analysis showed that this benefit was confined to those having salvage surgery (log rank test p = 0.0006); for those having surgery for claudication there was no significant benefit. No major bleeding events occurred in either group. We conclude that low-molecular weight heparin is better than aspirin and dipyridamole in maintaining femoropopliteal-graft patency in patients with critical limb ischaemia undergoing salvage surgery. This treatment should have considerable cost benefits. To evaluate the influence of antiplatelet drugs on patency in femoropopliteal vein bypasses, 48 vascular surgeons recruited 549 patients to a randomized double-blind trial of aspirin (300 mg) + dipyridamole (150 mg) or placebo twice daily starting 2 days before surgery and continuing indefinitely. Graft occlusion measured objectively by independent coordinators and cardiovascular events (myocardial infarction or stroke) were studied, expressed by life table, and analyzed statistically by log rank and confidence intervals (95% CI). Randomization achieved comparable groups with 60% of grafts inserted for rest pain or gangrene. Operative complications on aspirin plus dipyridamole included 18 reoperations for bleeding and 12 hematomas compared with 9 and 14, respectively, on placebo (NS). Most of the 172 graft failures occurred early with failure rates of 43/1000 patient-months in the first 3 months, reducing to 17/1000 at 6 to 12 months, and under 10/1000 in subsequent years. Cumulative graft patency on placebo was 72%, 62%, and 60% at 1, 2, and 3 years, respectively, compared with 78%, 70%, and 61% on aspirin plus dipyridamole. The difference in patency of 6.1% (95% CI, -3% to 15.5%) at 1 year and 8.0% (95% CI, -5% to 21%) at 2 years failed to achieve significance (p = 0.43). On mean follow-up of 34 months, 53 (132/1000 patient-years) cardiovascular events (myocardial infarction or cerebrovascular accident) occurred in patients on placebo compared with only 35 (73/1000) on aspirin plus dipyridamole, a significant difference of 59/1000 (p = 0.004). Antiplatelet therapy had little influence on femoropopliteal vein patency, but subsequent myocardial infarction and stroke was reduced in these patients with peripheral vascular disease. 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 randomised 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. 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.
                We conducted a randomized, 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.
                At 13 centers in the United States, 649 patients were randomly 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.
                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. (ClinicalTrials.gov number, NCT00067119.)
                2009 Massachusetts Medical Society Oral anticoagulants are better than aspirin for secondary prevention after myocardial infarction and after cerebral ischaemia in combination with non-rheumatic atrial fibrillation. The European/Australasian Stroke Prevention in Reversible Ischaemia Trial (ESPRIT) aimed to determine whether oral anticoagulation with medium intensity is more effective than aspirin in preventing future vascular events in patients with transient ischaemic attack or minor stroke of presumed arterial origin.
                In this international, multicentre trial, patients were randomly assigned within 6 months after a transient ischaemic attack or minor stroke of presumed arterial origin either anticoagulants (target INR range 2.0-3.0; n=536) or aspirin (30-325 mg daily; n=532). The primary outcome was the composite of death from all vascular causes, non-fatal stroke, non-fatal myocardial infarction, or major bleeding complication, whichever occurred first. In a post hoc analysis anticoagulants were compared with the combination of aspirin and dipyridamole (200 mg twice daily). Treatment was open, but auditing of outcome events was blinded. Primary analysis was by intention to treat. This study is registered as an International Standard Randomised Controlled Trial (number ISRCTN73824458) and with ClinicalTrials.gov (NCT00161070).
                The anticoagulants versus aspirin comparison of ESPRIT was prematurely ended because ESPRIT reported previously that the combination of aspirin and dipyridamole was more effective than aspirin alone. Mean follow-up was 4.6 years (SD 2.2). The mean achieved INR was 2.57 (SD 0.86). A primary outcome event occurred in 99 (19%) patients on anticoagulants and in 98 (18%) patients on aspirin (hazard ratio [HR] 1.02, 95% CI 0.77-1.35). The HR for ischaemic events was 0.73 (0.52-1.01) and for major bleeding complications 2.56 (1.48-4.43). The HR for the primary outcome event comparing anticoagulants with the combination treatment of aspirin and dipyridamole was 1.31 (0.98-1.75).
                Oral anticoagulants (target INR range 2.0-3.0) are not more effective than aspirin for secondary prevention after transient ischaemic attack or minor stroke of arterial origin. A possible protective effect against ischaemic events is offset by increased bleeding complications. 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 < or =3) were eligible. Randomization 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 infarction, 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. 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 prospective, randomized, double-blind, placebo-controlled, parallel group study to examine if dipyridamole and/or aspirin decreased the rate of thrombosis of expanded 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. Aprotinin (APR) reduces postoperative blood loss but may induce thrombosis. Dipyridamole (DIP) limits platelet aggregation and may reduce the thrombotic complications associated with APR.
                To evaluate the safety and effectiveness of combined APR and DIP, we undertook a prospective randomized trial in patients undergoing cardiac operations. Patients were stratified according to risk for bleeding (low or high), and received either DIP with placebo (DIP group; n = 59) or DIP with APR (DIP + APR group; n = 56). Blood samples were obtained for the measurement of hematologic and biochemical parameters. Blood loss and transfusion requirements were documented postoperatively.
                Postoperative blood loss and transfusion requirements were significantly lower in the DIP + APR group at 6, 12, and 24 hours after bypass (p < 0.01). No significant differences were found between groups in the incidence of perioperative mortality (DIP, 0%; DIP + APR, 3%), myocardial infarction (DIP, 0%; DIP + APR, 3%), stroke (DIP, 1%; DIP + APR, 1%), or potential thrombotic events (death, myocardial infarction, and stroke: DIP, 2%; DIP + APR, 5%). In addition, these rates did not differ from those of nonparticipating matched control patients.
                Administration of both drugs simultaneously was more effective than DIP alone in reducing postoperative blood loss. A platelet inhibitor may be required to reduce the thrombotic complications associated with APR. Further studies evaluating graft patency and perioperative ischemia are necessary to confirm the potential benefits of the combination of a platelet inhibitor and APR. Recent evidence has suggested that the delayed cerebral ischemic deficits that often follow surgery for aneurysmal subarachnoid hemorrhage (SAH) may be due to a proliferative vasculopathy. This vascular pathology may result from an interaction between the platelets and the vessel wall. A single-blind controlled trial of dipyridamole administration in 677 patients presenting with SAH (of whom 348 came to surgery) was undertaken to test the hypothesis that the modification of platelet behavior might reduce the incidence of ischemic deficits. Blind independent assessment of the outcome in the surgical group based on the Glasgow Outcome Scale and the specific neurological deficits revealed no significant differences between the control and treatment groups. Our aim was to determine the effect of short-term therapy with anti-platelet drugs on type-2 diabetic nephropathy for which a generally accepted therapy is missing.
                Seventy-six patients with type-2 diabetic nephropathy, who had normal renal function tests were randomized into the 4 groups; each group (n = 19) received one of the following treatments: aspirin (1000 mg), dipyridamole (750 mg), their combination or placebo daily for 2 months. Blood pressure, fasting blood sugar, serum electrolytes, creatinine clearance and 24 hours urine protein excretion rate was measured just before and at the end of the trial.
                Proteinuria and urinary protein: creatinine ratio decreased significantly in all 3 groups receiving aspirin and/or dipyridamole compared with the placebo group, also in each of those 3 groups comparing pre- and post-treatment values, while creatinine clearance rate, blood pressure, and blood sugar remained unchanged. At the end of the trial, the percentage proteinuria change was-15.9%,-14.8%,-37.3% and 1.9% in aspirin, dipyridamole, their combination and placebo groups respectively. The percentage proteinuria change had no positive correlation with demographic, clinical and laboratory findings but showed a strong positive correlation with mode of the therapy (r = 0.38, p = 0.0007). The percentage decline in proteinuria was significantly higher in the combination group than in the aspirin and dipyridamole groups. No side effects related to aspirin or dipyridamole was seen during the trial.
                Short-term trial of aspirin and/or dipyridamole significantly reduces proteinuria of type-2 diabetic nephropathy, with the most prominent effect seen with combination of the 2 drugs. To determine the effects of antiplatelet therapy among patients at high risk of occlusive vascular events.
                Collaborative meta-analyses (systematic overviews).
                Randomised trials of an antiplatelet regimen versus control or of one antiplatelet regimen versus another in high risk patients (with acute or previous vascular disease or some other predisposing condition) from which results were available before September 1997. Trials had to use a method of randomisation that precluded prior knowledge of the next treatment to be allocated and comparisons had to be unconfounded-that is, have study groups that differed only in terms of antiplatelet regimen.
                287 studies involving 135 000 patients in comparisons of antiplatelet therapy versus control and 77 000 in comparisons of different antiplatelet regimens.
                "Serious vascular event": non-fatal myocardial infarction, non-fatal stroke, or vascular death.
                Overall, among these high risk patients, allocation to antiplatelet therapy reduced the combined outcome of any serious vascular event by about one quarter; non-fatal myocardial infarction was reduced by one third, non-fatal stroke by one quarter, and vascular mortality by one sixth (with no apparent adverse effect on other deaths). Absolute reductions in the risk of having a serious vascular event were 36 (SE 5) per 1000 treated for two years among patients with previous myocardial infarction; 38 (5) per 1000 patients treated for one month among patients with acute myocardial infarction; 36 (6) per 1000 treated for two years among those with previous stroke or transient ischaemic attack; 9 (3) per 1000 treated for three weeks among those with acute stroke; and 22 (3) per 1000 treated for two years among other high risk patients (with separately significant results for those with stable angina (P=0.0005), peripheral arterial disease (P=0.004), and atrial fibrillation (P=0.01)). In each of these high risk categories, the absolute benefits substantially outweighed the absolute risks of major extracranial bleeding. Aspirin was the most widely studied antiplatelet drug, with doses of 75-150 mg daily at least as effective as higher daily doses. The effects of doses lower than 75 mg daily were less certain. Clopidogrel reduced serious vascular events by 10% (4%) compared with aspirin, which was similar to the 12% (7%) reduction observed with its analogue ticlopidine. Addition of dipyridamole to aspirin produced no significant further reduction in vascular events compared with aspirin alone. Among patients at high risk of immediate coronary occlusion, short term addition of an intravenous glycoprotein IIb/IIIa antagonist to aspirin prevented a further 20 (4) vascular events per 1000 (P<0.0001) but caused 23 major (but rarely fatal) extracranial bleeds per 1000.
                Aspirin (or another oral antiplatelet drug) is protective in most types of patient at increased risk of occlusive vascular events, including those with an acute myocardial infarction or ischaemic stroke, unstable or stable angina, previous myocardial infarction, stroke or cerebral ischaemia, peripheral arterial disease, or atrial fibrillation. Low dose aspirin (75-150 mg daily) is an effective antiplatelet regimen for long term use, but in acute settings an initial loading dose of at least 150 mg aspirin may be required. Adding a second antiplatelet drug to aspirin may produce additional benefits in some clinical circumstances, but more research into this strategy is needed. 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 prospective, 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 infarction 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. 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.
                In this double-blind, 2-by-2 factorial trial, we randomly 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 infarction, or death from vascular causes. Sequential statistical testing of noninferiority (margin of 1.075), followed by superiority testing, was planned.
                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).
                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. (ClinicalTrials.gov number, NCT00153062.)
                2008 Massachusetts Medical Society A randomised double-blind multicentre trial has been performed comparing the influence of 3 months prophylaxis with acetylsalicylic acid/dipyridamole (50 mg/400 mg daily) or placebo on the outcome following percutaneous transluminal angioplasty for lower limb ischaemia. Two hundred and twenty-three patients were included and followed. There were no differences between the groups regarding results 1, 3, 6 and 12 months following the dilatation treatment. It can be concluded that acetylsalicylic acid at the dose of 50 mg daily combined with dipyridamole does not seem to have a prophylactic effect after transluminal angioplasty during a follow-up period of 1 year. Patients (125) who had carotid transient ischemic attacks (TIAs) and one or more accessible carotid lesions visualized angiographically had reconstructive operations of the carotid artery and were then randomly assigned to aspirin or placebo treatment. The were followed to determine the incidence of subsecquent TIAs, death, cerebral infarction, or retinal infarction. Life table analysis (for 24 months follow up) that eliminated deaths which were not stroke-related revealed a significant difference in favor of aspirin. Because of the small number of patients and the short period of follow up, these results should be interpreted only as consistent with those reported in the initial publication but not conclusive of an aspirin effect in preventing cerebral infarction. To investigate whether anticoagulation or platelet inhibition treatment provides better prevention of reobstruction after percutaneous transluminal angioplasty (PTA).
                In a controlled study, 160 patients received either oral anticoagulants or a combination of low-dose acetylsalicylic acid (25 mg) and dipyridamole (200 mg) (ASAD) twice daily for 1 year after successful femoropopliteal PTA. Compliance was comparable. The patients in the two groups had similar clinical and angiographic characteristics. Patency was assessed with noninvasive methods 1 day and then 3, 6, and 12 months after PTA and was confirmed at angiography at the end of the study in 112 patients.
                Patency in patients who received anticoagulants was 53% and was not statistically significantly different from 69% in patients who received ASAD (P = .18). With anticoagulants, there were four bleeding complications (one was fatal); with ASAD, only five minor complications occurred.
                ASAD is at least as effective as anticoagulants for secondary prevention of obstruction after PTA but has less severe side effects.
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.