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Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The low-molecular-weight heparins (LMWHs) have been proven superior to placebo in reducing the incidence of acute coronary ischemic syndromes. Comparative studies vs. unfractionated heparin have not demonstrated superiority in favor of the LMWH dalteparin. In the Efficacy and Safety of Subcutaneous Enoxaparin in Non-Q-wave Coronary Events (ESSENCE) trial, enoxaparin was demonstrated to have a benefit over heparin. The results have contributed to a better understanding of the relative efficacy of LMWHs in acute coronary syndromes. A second trial with enoxaparin supported the conclusions of the ESSENCE trial. The antithrombotic effects of LMWHs have also been evaluated for the management of ischemic stroke with varied results. A trial assessing tinzaparin in acute ischemic stroke has completed enrollment, and its results may shed new light on the use of an LMWH for the management of stroke.
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PMID:Antithrombotics and anticoagulants in coronary syndromes and stroke. 1101 11

Acute stroke treatment using aspirin and/or heparin was studied in the International Stroke Trial (IST) and Chinese Acute Stroke Trial (CAST) which randomised over 40,000 patients altogether. Combining the results demonstrated that aspirin (150-300 mg) given within 48 h of the onset of stroke produced a small but significant improvement in outcome (death or dependency) 4 weeks to 6 months after stroke of about 1 patient per 100 treated. There was a significant reduction in recurrent ischaemic stroke of similar degree, which was not associated with significant increase in cerebral haemorrhage. Therefore, aspirin should be used as early secondary prevention against recurrent stroke, after excluding cerebral haemorrhage by scanning the patient. Heparin does not improve clinical outcome after stroke even in patients in atrial fibrillation. It decreased recurrent ischaemic stroke significantly in IST, but at the cost of a significant increase in cerebral haemorrhage. Low molecular weight heparins and heparinoids have not proved any more beneficial. Therefore, heparin does not appear to be a useful routine therapy in acute stroke. The use of heparin should, therefore, be limited to patients at high risk of deep vein thrombosis or early recurrence.
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PMID:Aspirin or heparin in acute stroke. 1109 90

Identification and treatment of the underlying risk factors for stroke reduce the potential for additional strokes; therefore, a thorough search for treatable risk factors is justified. Because some risk factors can have a cumulative effect, even children with known risk factors for stroke sometimes need to be evaluated for other conditions. Cerebral angiography is often helpful; I recommend angiography in any child with an unexplained infarction or hemorrhage. Angiography is especially important in children with intraparenchymal hemorrhage because more than one third of such children will prove to have some type of potentially treatable congenital vascular anomaly such as an arteriovenous malformation (AVM) or aneurysm. The evidence that periodic blood transfusion effectively prevents cerebral infarction due to sickle cell disease is compelling. Transfusions apparently must be continued indefinitely to maintain the reduction of stroke risk, and without iron chelation, chronic transfusion eventually results in severe iron toxicity and, most likely, death, so the decision to begin transfusion is not an easy one. Measurement of the time-averaged mean flow velocity in the large cerebral vessels with transcranial Doppler (TCD) is highly predictive of stroke risk in these children, enough to justify its routine use in screening patients with sickle cell disease for stroke risk. I believe that patients with sickle cell disease should be offered chronic transfusion after an initial large-vessel stroke or when the TCD results suggest a high risk of stroke. The family must be made aware of the serious complications of chronic transfusion and the importance of complying with chelation once it is started. There are no controlled clinical trials to guide the use of anticoagulants, antiplatelet agents, or thrombolytic agents in children, although these drugs are being used more and more often in pediatric patients. For the most part, our approach has been adapted from our experience with adults. Heparin followed by warfarin is often used for sinovenous thrombosis and for arterial dissection. I also suggest long-term anticoagulation for children with coagulopathy or a high risk of embolism due to congenital or acquired cardiac disease. It is reasonable to use a thrombolytic agent in children with an acute infarction; because few children present soon enough after the onset of symptoms, however, thrombolysis is infrequently used. Aspirin is used more than other antiplatelet agents in children, largely because of years of experience with aspirin and the lack of evidence that other agents are more effective. Despite its frequent use, there are no unequivocal indications for the use of aspirin in children. Aspirin is often started empirically in children suspected to be at substantial risk for additional ischemic stroke but whose risk is ill defined, an approach not too dissimilar from that often used in adult patients. Although the risk of Reye's syndrome in a child taking daily aspirin for stroke prevention is a common concern, I know of no published examples of children who developed Reye's syndrome while taking prophylactic aspirin. This apparently low risk must be weighed against the often-considerable risk of ischemic stroke that could be reduced by the use of daily aspirin. In situations such as vasculopathy or infarction of unknown cause, the small risk of Reye's syndrome seems acceptable.
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PMID:Stroke in Children. 1109 55

Older individuals contribute heavily to the percentage of deaths due to myocardial infarction (MI) and stroke. The incidence of venous thromboembolism (VTE) is highest in subjects > 65 years. Prospective intervention trials involving groups of clinically comparable subjects > or = 60 allow the following statements to be made with regard to the use of antithrombotic drugs in the elderly. Antiplatelet agents. To prevent recurrence of ischaemic stroke and MI in stable/unstable angina, MI, TIA/stroke or peripheral arterial disease, aspirin is the drug of choice. Clopidogrel is more effective than aspirin in this respect. Heparin. For the treatment of acute deep venous thrombosis (DVT) and pulmonary embolism (PE), intravenous standard heparin or subcutaneous standard heparin are effective (aPTT 1.5-2.0 times baseline values). As the risk of bleeding increases with age, low-molecular-weight heparins (LMWH) are preferable in the elderly. For the prophylaxis of VTE in general surgery in subjects at low-moderate risk, low-dose heparin or low doses of LMWH are effective. In subjects at high risk, adjusted-dose heparin plus physical devices or high-dose LMWH are recommended. The combination of heparin and aspirin is the standard treatment for unstable angina and non-Q wave MI. LMWH are as active as standard heparin in this indication. Vitamin K antagonists. For the chronic treatment of VTE, warfarin is also the treatment of choice (INR 2.0-3.0) in the elderly, though lower doses are needed due to their hypersensitivity to oral anticoagulants. For the prevention of thromboembolic stroke in patients > 75 with atrial fibrillation, warfarin is the drug of choice. Patients aged 65-75 may receive warfarin or aspirin. Thrombolytic agents. Thrombolytic agents are not recommended for treating DVT in the elderly because of their limited risk/benefit ratio and should be confined to massive PE. In the absence of contraindications, thrombolysis for MI may be considered in the elderly.
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PMID:Antithrombotic drugs for older subjects. Guidelines formulated jointly by the Italian Societies of Haemostasis and Thrombosis (SISET) and of Gerontology and Geriatrics (SIGG). 1138 24

Anticoagulation regimens vary according to surgeon, nature of the valve (mechanical or biological), its position and other risk factors for stroke. The American College of Chest Physicians (2001) have made the following recommendations to protect patients with prosthetic heart valves from developing a stroke: (i) For mechanical heart valves: Anticoagulation with Warfarin at an INR range 2-3 for patients with a bileaflet mechanical valve in the aortic position; (ii) in the mitral position, an INR of 2.5-3.5 is recommended; an alternative recommendation is an INR of 2-3 in combination with aspirin (80 mg/day); and (iii) in patients with a mechanical valve and a history of systemic embolization, an INR of 2.5-3.5 combined with low-dose aspirin (80-100 mg) is recommended; when Warfarin therapy is initiated, the doses for patients aged <70 years is 4 mg, and for patients aged >70 years it is 3 mg. While it is important to recognize that the therapeutic range for Warfarin is narrow, recommendations have also been established to manage patients with high INRs and for the temporary discontinuation of anticoagulant therapy when they undergo surgical procedures. Rapid anticoagulation can be achieved either with unfractionated heparin or with low-molecular weight heparin (LMWH). Heparin is initiated with an intravenous bolus of 80 U/kg bodyweight, and an infusion of 18 U/kg/h. The activated thromboplastin time should be 60-80 s. An alternative to intravenous heparin is subcutaneous LMWH, which is prescribed in a mg/kg dose. In the event of valve thrombosis in patients who are hemodynamically unstable, surgical exploration with thrombectomy is indicated, with or without valve replacement. In patients who are hemodynamically stable, thrombolytic therapy is recommended initially.
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PMID:Anticoagulation management of valve replacement patients. 1184 22

The development of treatments for acute neurodegenerative diseases (stroke and brain trauma) has focused on (i) reestablishing blood flow to ischemic areas as quickly as possible (i.e. mainly antithrombotics or thrombolytics for stroke therapy) and (ii) on protecting neurons from cytotoxic events (i.e. neuroprotective therapies such as anti-excitotoxic or anti-inflammatory agents for stroke and neurotrauma therapies). This paper reviews the preclinical data for enoxaparin in in vivo models of ischemia and brain trauma in rats. Following a photothrombotic lesion in the rat, enoxaparin significantly reduced edema at 24 h after lesion when the treatment was started up to 18 h after insult. Enoxaparin was also tested after an ischemic insult using the transient middle cerebral artery occlusion (tMCAO) model in the rat. Enoxaparin, 2 x 1.5 mg/kg i.v., significantly reduced the lesion size and improved the neuroscore when the treatment was started up to 5 h after ischemia. Enoxaparin, administered at 5 h after insult, reduced cortical lesion size in a dose-dependent manner. In permanent MCAO, enoxaparin (5 and 24 h after insult) significantly reduced lesion size and improved neuroscore. A slight and reversible elevation of activated partial thromboplastin time (APTT) suggests that enoxaparin is neuroprotective at a non-hemorrhagic dose. Traumatic brain injury (TBI) is often accompanied by secondary ischemia due in part to edema-induced compression of blood vessels. When enoxaparin, at 0.5 mg/kg i.v. + 4 x 1 mg/kg s.c., was administered later than 30 h after TBI, it significantly reduced edema in hippocampus and parietal cortex. At one week after TBI the lesion size was significantly reduced and the neurological deficit significantly improved in enoxaparin treated animals. Finally, the cognitive impairment was significantly improved by enoxaparin at 48 h to 2 weeks after TBI. The anticoagulant properties of unfractionated heparin and specifically enoxaparin can explain their anti-ischemic effects in experimental models. Furthermore, unfractionated heparin and specifically enoxaparin, have, in addition to anticoagulant, many other pharmacological effects (i.e. reduction of intracellular Ca2+ release; antioxidant effect; anti-inflammatory or neurotrophic effects) that could act in synergy to explain the neuroprotective activity of enoxaparin in acute neurodegenerative diseases. Finally, we demonstrated, that in different in vivo models of acute neurodegenerative diseases, enoxaparin reduces brain edema and lesion size and improves motor and cognitive functional recovery with a large therapeutic window of opportunity (compatible with a clinical application). Taking into account these experimental data in models of ischemia and brain trauma, the clinical use of enoxaparin in acute neurodegenerative diseases warrants serious consideration.
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PMID:Neuroprotective profile of enoxaparin, a low molecular weight heparin, in in vivo models of cerebral ischemia or traumatic brain injury in rats: a review. 1207 May 24

Family physicians should be familiar with the acute management of atrial fibrillation and the initiation of chronic therapy for this common arrhythmia. Initial management should include hemodynamic stabilization, rate control, restoration of sinus rhythm, and initiation of antithrombotic therapy. Part II of this two-part article focuses on the prevention of thromboembolic complications using anticoagulation. Heparin is routinely administered before medical or electrical cardioversion. Warfarin is used in patients with persistent atrial fibrillation who are at higher risk for thromboembolic complications because of advanced age, history of coronary artery disease or stroke, or presence of left-sided heart failure. Aspirin is preferred in patients at low risk for thromboembolic complications and patients with a high risk for falls, a history of noncompliance, active bleeding, or poorly controlled hypertension. The recommendations provided in this article are consistent with guidelines published by the American Heart Association and the Agency for Healthcare Research and Quality.
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PMID:Acute management of atrial fibrillation: Part II. Prevention of thromboembolic complications. 1272 47

Patients with acute ischemic stroke can be treated by intravenous thrombolysis within 3 hours or by intraarterial thrombolysis within 6 hours of symptom onset. Thrombolysis leads to an absolute reduction of a long term disability of 11-15% in selected patients. Aspirin is the drug of choice in most patients with acute stroke, if thrombolysis is contraindicated. Heparin is only used in acute stroke patients with high risk of recurrence. The diagnosis and treatment of medical and neurological complications remain crucial in the management of acute stroke.
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PMID:[Stroke as an emergency]. 1224 34

Aspirin is the drug of choice in most patients with acute stroke, if thrombolysis is contraindicated. Heparin is only used in acute stroke due to cerebral venous thrombosis, extracranial carotid or vertebral artery dissection and cardiac emboli with high risk of recurrence. In the prevention of recurrent stroke in patients with a noncardioembolic ischemic stroke antiplatelet agents are used. Aspirin is the first-line agent. Clopidogrel or a combination aspirin/dipyridamol are recommended for patients with several risk factors or recurrent cerebrovascular events. Warfarin has demonstrated a clear efficacy in stroke prevention in patients with atrial fibrillation, cerebral venous thrombosis and antiphospholipid antibody syndrome. Other, less well established possible indications for warfarin in the secondary prevention of stroke are symptomatic intracranial artery stenosis, large aortic atheroma, extracranial carotid or vertebral artery dissection and patent foramen ovale.
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PMID:[Anticoagulation and antiaggregation in neurological patients]. 1263 76

[2,3-dioxo-7-(1H-imidazol-1-yl)-6-nitro-1,2,3,4-tetrahydro-1-quinoxalinyl]-acetic acid monohydrate (YM872 or zonampanel), an AMPA receptor antagonist, is in clinical development for acute ischemic cerebral infarction. Stroke patients are prone to have subsequent intracerebral hemorrhages. In order to predict potential adverse effects, YM872 was tested in a rat model with collagenase-induced intracerebral hemorrhage. The morphologically determined hematoma volumes after 24 h were compared between animal groups intravenously infused with 3600 U/kg/h heparin for 30 min, or with 20 or 40 mg/kg/h of YM872, or placebo for 4 h. Heparin enlarged hematoma volume, but neither dose of YM872 affected hematoma size. In a separate study, neurological deficits were scored at various days after intracerebral hemorrhage induction in animals with intravenous infusion for 24 h of 10 or 20 mg/kg/h YM872, or saline. The YM872 groups scored significantly better than the saline group at 14 days. These data suggest that YM872 does not exacerbate intracerebral hemorrhage and might accelerate recovery.
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PMID:Effect of AMPA receptor antagonist YM872 on cerebral hematoma size and neurological recovery in the intracerebral hemorrhage rat model. 1270 61


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