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Chronic peripheral arterial disease (PAD) is frequently treated by implantation of either an infrainguinal autologous venous or artificial graft. One-year occlusion rates for infrainguinal bypasses vary between 15 and 75%, depending on the site of distal anastomosis, length, quality, and material of the graft, but also on other factors such as proximal inflow and distal outflow conditions. To prevent graft occlusion, patients are usually treated with either an antiplatelet or antithrombotic drug, or a combination of both. Little is known about which drug is optimal to prevent infrainguinal graft occlusion.
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A virtually nationwide survey was performed among Hungarian neurologists involved in stroke care, who responded to a questionnaire concerning the use of antiplatelet agents and anticoagulation in acute ischemic stroke and for secondary prevention.
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Antiplatelet therapy plays a crucial role in the primary and secondary prevention of noncardioembolic ischemic stroke / transient ischemic attacks (IS/TIA). Several antiplatelet agents are available. This review deals with the characteristics of particular antiplatelet agents as well as choice of antiplatelet treatment in various situations, based on the evidence and international recommendations.
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MBF and CVR were measured using 150-water positron emission tomography in 24 patients after stroke or transient ischemic attack, before and 6.7 +/- 1.9 days after starting the dipyridamole/aspirin combination (Aggrenox) therapy.
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.
Thirty-five patients with gangrene or pregangrene of the feed associated with palpable peripheral pulses have been treated with the platelet suppressive drugs aspirin and dipyridamole. Sulphinpyrazone was substituted for two patients who could not tolerate aspirin. Complete reversal of the signs and symptoms occurred in more than 50% of the treated patients. Recurrence of pain occurred in the five patients in whom antiplatelet therapy was discontinued. Reversal of symptoms was again achieved by reintroduction of the drugs. An increased incidence of spontaneous platelet aggregation and hypersensitive platelets was observed in those patients who responded to platelet suppressive therapy. These results indicate that platelet suppressive therapy is of therapeutic value in selected patients with peripheral gangrene.
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A combined MEDLINE and manual search was made for relevant articles from 1966 to November 1999. Standard meta-analysis techniques were used.
A total of 7612 patients (five trials) were included in the analyses, 3800 allocated to A+D and 3812 to ASA alone. The trial-adjusted hazard ratio (HR) for the composite event of vascular death, non-fatal myocardial infarction and non-fatal stroke was 0.82 (95% confidence interval (CI) 0.72 to 0.92). HRs did not differ in subgroup analyses based on age, sex, qualifying event, hypertension, diabetes, previous stroke, ischaemic heart disease, aspirin dose, type of vessel disease and dipyridamole formulation, nor across baseline risk strata as assessed with two different risk scores. A+D were also more effective than ASA alone in preventing recurrent stroke; HR 0.78 (95% CI 0.68 to 0.90).
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Twenty patients suffering from transient attacks of ischaemia were studied. Seven received acetylsalicylic acid, six dipyridamole and seven a combination of the two drugs. No significant difference in platelet aggregation was shown in the acute phase between the three treatment groups using an adenosine diphosphate test method. Using Thrombofax platelet substitute, however, a significant difference was seen in all measures. On the seventh day following the ischaemic attack the Thrombofax values returned to normal but, in contrast, Platelet Factor 4 release was increased. Monthly testing of platelet activity during treatment shows that the combination of acetylsalicylic acid with dipyridamole was more effective in bringing about an early inhibition of Platelet Factor 4 release than either agent alone.
Orally administered dipyridamole/aspirin combination therapy in secondary stroke prevention increases MBF and decreases CVR significantly. These cardiac side effects of the dipyridamole/aspirin combination should be taken into account in stroke patients with proven or suspected coronary artery disease, particularly in combination with a small body surface area.
Out of 235 patients with recent cerebral transient ischaemic attacks, 208 subjects were available for final evaluation after 6 months' randomised treatment with either pentoxifylline (PTX 1200 mg/day) or a combination (ASAD) of acetylsalicylic acid (ASA, 1050 mg/day) and dipyridamole (D, 150 mg/day). Prevention of TIA, stroke or death attributable to previous events were endpoint criteria. The pentoxifylline group (n = 100) exhibited no recurrent episodes in 86 patients (86%). TIA occurred in 9 patients, stroke in 5 patients and there was 1 death. In the ASAD group (n = 108) no recurrence of ischaemic episodes was recorded in 82 cases (75.9%). TIA occurred in 20 patients, stroke in 6 patients and there were 3 deaths of vascular origin. Side effects were recorded in 4 ASAD and 1 PTX patients. The total rate of recurrence was 14% with PTX as compared to 24.1% with ASAD treatment.
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Eight patients with livedo vasculitis of four to 30 years' duration that was unresponsive to a variety of medications were treated with pentoxifylline. Three patients experiences complete healing and remained free of active lesions while receiving the drug, four noted much improvement, and one had no change.
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A different rate and timing of subacute stent thrombosis after percutaneous coronary intervention was reported with various peri-interventional antithrombotic regimens. Next to platelet activation, coagulation triggered by tissue factor (TF) may play a key role in this process. Thirty-one consecutive patients with stable and unstable angina undergoing coronary stenting were randomly assigned to adjunct oral anticoagulation/anti-platelet therapy (coumadin, dipyridamole, aspirin and heparin; n = 16) or adjunct anti-platelet therapy with thienopyridin (ticlopidine, aspirin and heparin; n = 15). Antigen levels of plasma TF, total tissue factor pathway inhibitor (TFPI) and TFPI/ activated factor X (TFPI/FXa) complex were determined before and for up to 6 days after intervention by immunoassay. At baseline, significantly higher levels of plasma TF and TFPI/FXa were found in patients with unstable angina [TF, 161 pg/ml (126-191 pg/ml); TFPI/FXa, 7.8 ng/ml (6.1-9.6 ng/ml)] compared with stable angina [TF, 62 pg/ml (46-82 pg/ml), P < 0.0001; TFPI/FXa, 4.5 ng/ml (3-7.6 ng/ml), P= 0.003]. One hour after intervention, an increase of plasma TF and TFPI/FXa was seen in both treatment groups. In unstable angina patients, plasma levels of TF, TFPI and TFPI/FXa were more efficiently reduced by adjunct ticlopidine therapy compared with adjunct coumadin/dipyridamole. These data suggest reduced release of circulating TF by combined anti-platelet therapy with ticlopidine and aspirin after coronary artery stenting, which may-contribute to the lower incidence of subacute stent thrombosis previously observed.
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To define current practice regarding the use of pharmacological prophylaxis to prevent postoperative graft occlusion.
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174 ischemic stroke patients with a mean age of 70.3 years, 63% men and 37% women, were recruited. Headache of any kind was reported in 70 patients (40.2%) and 37 (21.3%) assessed the headache as moderate/severe. Six patients stopped medication due to headache. A subsiding character of the headache was found with a mean of 3.1 days. Patients with TIA had a significantly higher risk of getting headache compared to manifest stroke, regardless of localization. There was a trend towards higher risk in younger age groups and females. No effect was seen on the number of days since stroke onset.
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On the basis of the results of the European stroke Prevention Study (ESPS 2) obtained on 6,602 patients, we used a Markov model to perform a cost-effectiveness analysis of a combination of a low-dose of acetylsalicylic acid (ASA) (25 mg b.i.d.) and sustained-release dipyridamole (DP) (200 mg b.i.d.) versus a low-dose of acetylsalicylic acid alone in the prevention of recurrent stroke in Belgium. The perspective was that of the Social Security. Total costs per patient over 5 years amounted to 1,317,718 FB for placebo, 1,312,015 FB for ASA and 1,326,526 FB for ASA-DP, with respectively 3.16, 3.25 and 3.33 stroke-free life years (SFLY). For 1,000 patients followed over 5 years, the number of SFLYs gained by ASA-DP is 170 when compared to placebo and 100 when compared to ASA. As compared to placebo, ASA is a dominant strategy and the combination AAS-DP has a cost-effectiveness ratio of 50,569 FB per SFLY gained. The cost-effectiveness ratio of ASA-DP vs. ASA was 176,963 FB per SFLY gained and was not substantially modified in sensitivity analyses. The favourable cost-effectiveness ratio for ASA-DP is mainly explained by the reduction of costs associated with the acute treatment of stroke.
ninety-seven patients were identified. Mean follow-up time was 26 months. The annual risk of (non-)fatal stroke was 5.3% for all strokes (95% CI 2. 9%-9.6%) and 3.8% for ipsilateral stroke (95% CI 1.9%-7.7%). Hyperlipidaemia and severe stenosis of the contralateral ICA were independent risk factors. Twenty-two of 32 patients with a severe stenosis of the contralateral ICA underwent CEA, of which one patient died and three suffered a minor ischaemic stroke. The perioperative risk of CEA in the control group of 20 patients with asymptomatic contralateral ICA occlusion was 0% (0 of 20).
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Systematic assessment of the literature.
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The American College of Chest Physicians (ACCP) recommends aspirin 50-325 mg/d to be the initial antiplatelet of choice for the prevention of atherothrombotic cerebral ischemic events. However, with the favorable results of the ESPS-2, it may be appropriate to substitute aspirin/ER dipyridamole for aspirin alone as the drug of choice. This combination appears to have a favorable adverse effect profile. The relative effectiveness of aspirin/ER dipyridamole compared with clopidogrel and ticlopidine has yet to be determined. If alternative antiplatelet therapy is needed, the ACCP recommends clopidogrel rather than ticlopidine because of its lower incidence of adverse effects. The ACCP further states that the combination of aspirin plus dipyridamole may be more effective than clopidogrel; these agents have a similarly favorable adverse effect profile.
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The primary outcome measure of efficacy was serious vascular events (non-fatal stroke, non-fatal myocardial infarction and vascular death). The outcome measure of safety was any bleeding.
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We report a case of thrombotic thrombocytopenic purpura which responded spectacularly to therapy consisting of corticosteroids, prostacyclin, high doses of platelet anti-aggregants and repeated plasma exchange. There was no anomaly of the von Willebrand factor VIII. The number of schizocytes and the lactate dehydrogenase level are as important as the beta-thromboglobulin dosage.
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Stroke is the third leading cause of death in the US with recurrent events a high likelihood in those who survive an initial event. The long-term goal of therapy is to prevent the recurrence of stroke and other atherosclerotic events. Aspirin has been the first-line agent for stroke prevention for a long time. As new antiplatelet agents have been introduced, their role in the secondary prevention of stroke remains to be defined. In particular, the role of the combination of aspirin and modified-release dipyridamole (Aggrenox, Boehringer Ingelheim Corp.), the newest product, in the secondary prevention of stroke, remains unknown. The purpose of this manuscript is to review the evidence of these antiplatelet agents in the secondary prevention of stroke and arrive at a conclusion specifically regarding the role of Aggrenox. Clinical studies which examined stroke as a single primary outcome or as one event in a combined primary outcome will be reviewed.
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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 infarction 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 randomly 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.