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Older TBI patients on preinjury ACAP agents experience a comparatively higher rate of inpatient mortality and other adverse outcomes caused by the effects of antiplatelet agents. Our findings should inform decision making regarding prognosis and caution against grouping anticoagulant and antiplatelet users together in considering outcomes.
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Kawasaki Disease (KD) is an acute systemic vasculitic disorder of childhood of unknown etiology. Initially KD was thought to be a benign disease, but later on it became obvious that cardiac manifestations are present in about 25-30% of patients and lead to death in about 0.5-2% of them. An early diagnosis and treatment are important to avoid an unfavourable prognosis. In recent years, a number of publications described patients in which the diagnosis was delayed because they did not fulfil the required criteria of KD. These forms of KD are known as atypical or incomplete KD. The aim of this work is to describe two cases of atypical KD observed at the Department of Pediatrics, University of Pisa during the year 1992.
A total of 125 patients undergoing aorta-coronary bypass grafting for disabling angina were randomized to receive either 330 mg of acetylsalicylic acid (aspirin) plus 75 mg of dipyridamole three times daily or a placebo for 6 months postoperatively. In addition, all patients were given warfarin for 3 months. Repeat angiography was performed at 6 months in 103 patients. In the treatment group 95 grafts were implanted in 48 patients, of which 87 were patent (91.6% patency rate). This figure compares with 88 grafts patent out of 118 implanted in 55 patients in the placebo group (74.6% patency rate) (p less than 0.01). We conclude that antiplatelet therapy improves the early patency of saphenous vein aorta-coronary bypass grafts.
156 patients with transient ischemic attacks (TIA) or reversible ischemic neurological deficit (RIND) were given prophylactic anticoagulant (AC) treatment against cerebral infarction in a prospective multicenter study from 5 hospitals in southern Sweden. After 2 months of AC treatment, 135 patients remained in the study and were randomized into 2 groups; one continued with AC treatment and one changed to anti-platelet therapy. The patients were followed for 12 months. No significant difference was seen between the 2 groups but 3 completed cerebral infarctions occurred during anti-platelet therapy against one during AC treatment. One cerebral hemorrhage was seen during AC treatment. All completed strokes occurred in men who initially had carotid symptoms. The number of patients with TIA/RIND was somewhat higher in the anti-platelet group whereas myocardial infarctions occurred more often during AC treatment. Compared to the natural history of untreated TIA/RIND both treatments were found to have a prophylactic effect against cerebral infarction.
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Dipyridamole and in particular dipyridamole in combination with low-dose aspirin are very effective in preventing recurrent stroke. However, the mechanism(s) underlying this dipyridamole effect have not been elucidated. Since dipyridamole inhibits the cGMP-specific phosphodiesterase type V in vitro, we hypothesized and tested whether therapeutically relevant dipyridamole concentrations enhance NO/cGMP-mediated effects in intact human platelets studied ex vivo.
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A Medline and Pubmed literature search (January 1966 to February 2003) was conducted to identify articles relating APT and POAD. Manual cross referencing was also used.
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Antiplatelet therapy with dipyridamole, 100 mg q.i.d., starting 2 days before surgery, followed by aspirin, 325 mg t.i.d. plus dipyridamole, 75 mg t.i.d., 7 hours after surgery was assessed in the prevention of saphenous vein bypass graft occlusion. Early (less than or equal to 1 month) and late (1 year) occlusions were reduced both on a per patient and a per distal anastomosis basis. Bleeding complications were not increased. Graft occlusion in high-risk situations (low-flow grafts and endarterectomy) was reduced, but not eliminated, by this antiplatelet regimen. The authors recommend this combination of dipyridamole before surgery, adding aspirin after surgery, to prevent coronary artery bypass graft occlusion.
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To determine the drug dose required to inhibit platelet reactivity by at least 50%, 2 drug regimens were evaluated in heartworm-negative, heartworm-infected, and heartworm-infected dogs embolized with dead heartworms. Aspirin, or a combination of aspirin and dipyridamole, were administered to 2 groups of Beagles (n = 5 each) for 5 to 9 days; a third group of 5 Beagles served as nontreated controls. For heartworm-negative dogs, mean (+/- SD) aspirin dosage that inhibited collagen-induced platelet reactivity by at least 50% was 6 (+/- 2) mg/kg of body weight given once daily. The aspirin/diphridamole combination dosage was 1 mg of each drug/kg given every 12 hours. All dogs (n = 15) were implanted with 7 adult heartworms each and remedicated (or not treated) beginning at 21 days after heartworm implantation. In heartworm-infected dogs, mean aspirin dosage required to inhibit collagen-induced platelet reactivity greater than or equal to 50% was 10 (+/- 6) mg/kg. Mean dosage of aspirin/dipyridamole combination was 1.6 +/- (0.5) mg of each drug/kg given every 12 hours. When platelet reactivity in response to collagen was determined to be inhibited by at least 50% in all medicated dogs, each dog (n = 15) was embolized with 7 dead adult heartworms to mimic heartworm adulticidal treatment. Platelet reactivity was monitored for 21 days after treatment, and drug dose was adjusted to maintain platelet inhibition by at least 50%. In embolized dogs, mean aspirin dosage was 17 (+/- 14) mg/kg given once daily. Mean dosage of the aspirin/dipyridamole combination was 2.8 (+/- 1.3) mg of each drug/kg given every 12 hours. All dogs (n = 15) were euthanatized 21 days after heartworm embolization. Each lung lobe was evaluated for severity of lesions and presence of organized or fibrinous thrombi. Lesion severity in the aspirin- and aspirin/dipyridamole-treated dogs was not significantly different from that in control dogs.
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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).
We studied a retrospective cohort of adult patients with a diagnosis of IE who presented to the Mayo Clinic (Rochester, MN) during 1980-1998. The cohort was divided into 2 groups on the basis of whether they had received continuous daily antiplatelet therapy for at least 6 months prior to the time of hospitalization for IE. Antiplatelet therapy included aspirin, dipyridamole, clopidogrel, ticlopidine, or any of combination of these agents. The primary end point was a symptomatic embolic event that occurred prior to or during hospitalization. Multivariable logistic regression was used to assess the impact of continuous daily antiplatelet therapy on risk of symptomatic emboli associated with IE.
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Secondary prevention of stroke and other manifestations of atherothrombosis is essential if the burden of disease associated with these events is to be reduced. Therefore, it is important to identify patients most likely to benefit from antiplatelet therapy. There is a good rationale for combining antiplatelet agents with different modes of action, since different signalling pathways contribute to platelet activation. Based on the promising results obtained with an adenosine diphosphate receptor antagonist-aspirin combination in coronary stenting, several additional trials with clopidogrel plus aspirin are ongoing. They include CURE (Clopidogrel in Unstable angina to prevent Recurrent Events, in unstable angina and non-Q-wave myocardial infarction) and COMMIT (in acute myocardial infarction), which compare clopidogrel with placebo in patients receiving aspirin, and CREDO (Clopidogrel for Reduction of Events During extended Observation), a 1-year treatment follow-up to the clopidogrel arms of the CLASSICS trial (Clopidogrel Aspirin Stent International Cooperative Study). Planned trials with clopidogrel in neurology include SPS3 (Secondary Prevention of Small Subcortical Strokes, in patients with symptomatic lacunar stroke), and MATCH (Management of Atherothrombosis with Clopidogrel in High-risk patients, in patients with stroke or transient ischaemic attack plus one additional risk factor), which will compare the efficacy of clopidogrel plus aspirin versus clopidogrel in reducing important ischaemic events. Combination therapy with an oral glycoprotein (GP) IIb/IIIa receptor antagonist plus aspirin has so far been less promising. Trials of three compounds--orbofiban, xemilofiban and sibrafiban--in combination with aspirin for secondary prevention in cardiac patients have reported increased mortality compared with aspirin alone. A similar effect was seen when sibrafiban monotherapy was compared directly with aspirin alone. Trials of newer oral GP IIb/IIIa inhibitors are under way or are planned. The combination of dipyridamole plus aspirin appears to be superior to aspirin alone for the prevention of stroke in patients with stroke or transient ischaemic attack; the effectiveness of this combination is being further investigated in ESPRIT (European/Australian Stroke Prevention in Reversible Ischaemia Trial).
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A total of 2500 patients who had had one or more transient ischemic attacks or cerebral infarctions participated.
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It is unknown whether the addition of dipyridamole to aspirin as pretreatment for patients undergoing percutaneous transluminal coronary angioplasty (PTCA) decreases acute complications. In this study 232 patients were prospectively randomized to receive either aspirin 325 mg orally 3 times daily (group 1, n = 115) or aspirin 325 mg orally 3 times daily plus dipyridamole 75 mg orally 3 times daily (group 2, n = 117) before elective PTCA. All clinical, angiographic and PTCA-related variables were similar between groups. Angiographic success rate was 93% in both groups. Clinical success was achieved in 107 patients (92%) in group 1 and in 101 patients (88%) in group 2 (difference not significant). Q-wave myocardial infarction occurred in 2 patients (1.7%) in group 1 and 5 patients (4.3%) in group 2 (difference not significant). Emergency coronary artery bypass grafting was required in 3 patients (2.6%) in group 1 and 7 patients (6.1%) in group 2 (difference not significant). There was 1 in-hospital death (in group 2). In this study, the addition of dipyridamole to aspirin as pretreatment of patients undergoing PTCA did not significantly reduce acute complications compared to aspirin alone.
Six patients with no hemodynamically significant atherosclerotic lesions of the lower limb arteries but with ischemic changes of the feet or toes were studied and diagnosed as having atherothrombotic microembolism. All patients were non claudicators and had peripheral Doppler examinations on admission. Five patients experienced more than one separate episode of microembolization involving both extremities. None presented with a history of heart disease or diabetes. Biplanar arteriograms revealed in every case atherosclerotic degeneration of the aorta without any obstructing lesions and anatomical arterial continuity between the aorta and the site of distal embolization. Three patients who refused operation, were treated conservatively, with a combination of dipyridamole plus aspirin. Three other patients had surgical repair of their atheromatous infrarenal aorta: in two cases thromboendarterectomy was performed, and in the other a Dacron bifurcated graft interposition. No amputations resulted in the patients treated medically, but one of the surgical group lost one toe. This study confirms that atherothrombotic microembolism from an ulcerated atherosclerotic aorta is a potential threat to the extremities and indicates that the optimal therapy for this syndrome has yet to be found.
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The synergism of ASA and DIP in antiplatelet therapy was confirmed, as well as the important enhancing effect exerted by red cells.
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The Second European Stroke Prevention Study (ESPS2) was a randomized, placebo-controlled trial that investigated the efficacy of low-dose acetylsalicylic acid (ASA) and modified-release dipyridamole (DP), alone or in combination, in the secondary prevention of ischemic stroke. The trial demonstrated that the combination was significantly more effective than either agent used alone. The aim of the present study was to evaluate the influence of age on the efficacy of ASA and DP, alone or in combination, in the secondary prevention of stroke in the ESPS2 population.
Randomised controlled trials comparing antenatal antithrombotic therapy (either alone or in combination with other agents) with placebo or no treatment, or any other treatment in the antenatal period to improve maternal or infant health outcomes in women considered at risk of placental dysfunction.
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Research on the benefits of aspirin combined with other antiplatelet regimens for stroke prevention has yielded inconclusive results. Early trials of aspirin plus dipyridamole (DP) were unable to detect a significant benefit for combination therapy over aspirin alone, although they clearly demonstrated the value of combination therapy compared with placebo. Early trials such as the AICLA (Accidents ischémiques cérébraux liés a l'athérosclérose) trial and the American-Canadian Cooperative Study lacked the statistical power to detect differences in the benefit of combination versus monotherapy because of the small number of events in each treatment group. The Antiplatelet Collaboration, in its meta-analysis published in 1994, also failed to detect a significant difference between the benefit of aspirin plus DP and that of aspirin alone for the combined end point of stroke, myocardial infarction, and vascular death. The large European Stroke Prevention Study 2 (ESPS-2) trial recently provided evidence that aspirin plus DP does lead to a significantly greater reduction than aspirin alone. The 6,602 patient trial randomized patients into four treatment groups: aspirin (50 mg daily) plus sustained-release DP (400 mg daily), aspirin alone, DP alone, or placebo. The trial found that low-dose aspirin plus DP more than doubled the reduction in stroke risk achieved with aspirin alone, a 37% risk reduction for the combination versus 18.1% for aspirin alone. The results also suggest that the effects of aspirin and DP are additive.