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

The aim of this study is to determine whether a selective thrombin inhibitor, Argatroban, would prevent neuronal cell death and whether extra-mild hypothermia (35 degrees C) would enhance the neuroprotective effect of a selective thrombin inhibitor following transient focal ischemia in rats. Sprague-Dawley rats were subjected to MCAo using an intraluminal suture technique for 2 hrs. The rats were reperfused for 24 h and decapitated for infarct and edema analysis. Argatroban-treated animals received a continuous injection of argatroban (3.0 mg/kg) for 24 hrs after onset of ischemia, while vehicle-treated groups received same dose of vehicle. During ischemia, temporal muscle and rectal temperatures were monitored and maintained at 37 degrees C in the normothermic animals and at 35 degrees C in the hypothermic animals. Argatroban ameliorated the cortical ischemic damage significantly (p < 0.05). Moreover, argatroban with mild hypothermia decreased the cortical infarct or edema volume significantly compared with those of groups I and III (p < 0.05). Argatroban improved neurological symptoms significantly and also improved survival rate. These results demonstrate that extra-mild hypothermia (35 degrees C) enhances neuroprotective effects of a selective thrombin inhibitor, argatroban, suggesting that this combined therapy may be a new therapeutic strategy for the treatment of acute stroke.
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PMID:Mild hypothermia enhances the neuroprotective effects of a selective thrombin inhibitor following transient focal ischemia in rats. 1475 34

The emergence of novel antithrombotic agents may have a dramatic impact on anticoagulation clinics and other providers of anticoagulation services. Of the novel agents currently in development, the oral direct thrombin inhibitor ximelagatran shows the most promise as an agent to improve the field of oral anticoagulation management because it is easier and more convenient to use than warfarin. Ximelagatran is currently being investigated for several indications, including prophylaxis of venous thromboembolism in patients undergoing orthopedic surgery, venous thrombosis treatment, stroke prevention in atrial fibrillation, and acute coronary syndromes. Anticoagulation clinics presently provide systematic, organized management of oral anticoagulation therapy (warfarin in the US) and provide better patient outcomes than usual medical care. The introduction of ximelagatran in patient management may dramatically alter the workload dynamics in anticoagulation clinics. Clinics that will survive the introduction of novel agents will most likely shift from a main focus of warfarin monitoring to thrombotic disease management and coordination of all antithrombotic therapy. Comprehensive Antithrombosis Centers (CAC) will most likely manage patients with thrombotic disorders treated with a range of anticoagulant therapies.
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PMID:The future of anticoagulation clinics. 1476 Feb 14

OBJECTIVES: Ximelagatran is a novel oral direct thrombin inhibitor. It has favorable pharmacodynamic properties, with a broad therapeutic range without the need for anticoagulation monitoring. We aimed to discover whether ximelagatran offers a genuine future replacement to warfarin for patients in persistent atrial fibrillation (AF). MATERIALS AND METHODS: We provide an evidence-based review of the relative merits and disadvantages of warfarin and aspirin. We subsequently present an overview of the evidence for the utility of ximelagatran in the treatment of AF. RESULTS: Adjusted dose warfarin is recommended over aspirin for patients in AF at high risk of future stroke. Some of this benefit is partially offset by the higher bleeding risks associated with warfarin therapy. The SPORTIF III and V studies have shown that ximelagatran is not inferior to warfarin in the prevention of all strokes in patients with AF (both persistent and paroxysmal). This benefit was partially offset by the finding of a significant elevation of liver transaminases (>3 x normal) in 6% of patients. CONCLUSIONS: Current data would suggest that ximelagatran might represent a future alternative to warfarin. The lack of need for anticoagulant monitoring has been partially offset by a need for regular monitoring of liver function. Further data from randomized clinical trials is clearly needed.
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PMID:Anticoagulation for non-valvular atrial aibrillation - towards a new beginning with ximelagatran. 1510 1

The oral direct thrombin inhibitor ximelagatran (Exanta, AstraZeneca) is rapidly absorbed, is efficiently bioconverted to the active form, melagatran (AstraZeneca) and has shown efficacy and relative safety as an anticoagulant for prophylaxis and therapy of thromboembolism. Two Phase III trials, Stroke Prevention using an ORal Thrombin Inhibitor in atrial Fibrillation (SPORTIF V), have tested the hypothesis that oral ximelagatran, administered 36 mg twice daily without coagulation monitoring or dose adjustment, prevents stroke and systemic embolism at least as effectively as adjusted-dose warfarin (international normalized ratio, 2.0-3.0) in patients with nonvalvular atrial fibrillation. Both were randomized, multicenter trials (n > 3000 per trial) with blinded end-point assessment. The open-label SPORTIF III trial confirmed the noninferiority of ximelagatran versus warfarin. Publication of the full results from SPORTIF V is pending.
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PMID:Antithrombotic therapy in atrial fibrillation: ximelagatran, an oral direct thrombin inhibitor. 1515 65

A meta-analysis by the Antithrombotic Trialists' Collaboration showed significant reduction of vascular events including stroke. MI, and vascular death by antiplatelet therapy in high risk patients with obstructive vascular disease. Low dose aspirin of 75 to 150 mg was most effective and its very low dose below 75 mg was not proven effective. Cilostazol significantly reduced the risk of recurrence in Japanese patients with ischemic stroke, mostly lacunar stroke. Large randomized controlled trials (RCTs) such as MATCH, ACTIVE, and CHARISMA are ongoing to see an effect of aspirin plus clopidogrel. Among patients with non-valvular atrial fibrillation (NVAF), warfarin is recommended in patients at age over 75 years, and those with history of stroke or TIA, hypertension, congestive heart failure, diabetes or coronary heart disease, while aspirin can be alternative in patients without any of these risk factors of stroke. Target INR of 2.0 to 3.0 is recommended in these NVAF patients, although lower INR of 1.6 to 2.5 is recommended to avoid hemorrhagic stroke in elderly patients with NVAF. SPORTIF was conducted to compare ximelagatran, an oral thrombin inhibitor, with warfarin in NVAF patients with risk factors, and the result showed a comparable efficacy and safety of ximelagatran. WARSS did not show any efficacy of warfarin over aspirin in any subtypes of ischemic stroke patients without NVAF, acute MI, left ventricular thrombi, or prosthetic heart valve. PICSS, a substudy of WARSS, also did not show any efficacy of warfarin over aspirin in stroke patients with patent foramen ovale (PFO), although warfarin might be recommended in PFO patients with deep vein thrombosis.
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PMID:[EBM of cerebral infarction: message from mega-studies]. 1515 93

Ximelagatran (Exanta, AstraZeneca) is a novel oral direct thrombin inhibitor that inhibits the final step in the coagulation process - namely, the conversion of fibrinogen to insoluble fibrin by thrombin. Recently completed large clinical trials have evaluated the efficacy and safety of ximelagatran compared to standard anticoagulation therapy with warfarin and heparins in several thrombotic disorders including the treatment and prevention of venous thromboembolism following major orthopaedic surgery; stroke prevention in atrial fibrillation; and after acute myocardial infarction. This article reviews these recent clinical trials and explores the therapeutic potential of ximelagatran to become the oral anticoagulant of first choice in medicine.
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PMID:The therapeutic potential of ximelagatran to become the anticoagulant of choice in medicine: a review of recently completed clinical trials. 1516 85

Ximelagatran is the first orally available direct thrombin inhibitor. Ximelagatran is a pro-drug with an antithrombotic effect comparable to that of warfarin. Clinical studies have demonstrated that ximelagatran is as effective as warfarin in the prevention of deep-vein thrombosis, of stroke in patients with nonvalvular atrial fibrillation, and of the adverse cardiovascular events in patients with recent myocardial infarction. Ximelagatran can be administered without any need of laboratory test.
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PMID:[Ximelagatran: a promising new drug for oral anticoagulation]. 1521 35

The new oral direct thrombin inhibitor ximelagatran is at least equivalent to warfarin for stroke prevention in patients with non-valvar atrial fibrillation, and seems to be a promising adjunct to aspirin after acute coronary syndrome
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PMID:Will oral antithrombin agents replace warfarin? 1525 41

More than 8,000 researchers, clinicians and exhibitors from around the world gathered in San Francisco for the American Academy of Neurology 56th Annual Meeting, April 24 to May 1, 2004. Of the 1,300 studies at the conference, researchers presented more than 200 abstracts each on multiple sclerosis, stroke and dementia, 145 on epilepsy, 159 on Parkinson's disease, 132 on pain and about 50 each on tremor and dystonia. The use of brain imaging technology also figured strongly in the program, with 300 abstracts that mentioned magnetic resonance imaging and 50 that included positron emission tomography. Highlights included promising Parkinson's disease studies involving gene therapy and treatments using glial-cell-derived neurotrophic factor, but also new evidence of cardiac valve regurgitation associated with pergolide. Other highlights included studies on neural repair, new guidelines for the treatment of epilepsy and important studies comparing the thrombin inhibitor ximelagatran to warfarin for the prevention of stroke.
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PMID:New developments in the treatment of neurological diseases. 1533 92

Traditional anticoagulants have drawbacks that make them complex to manage, limit their usefulness, and increase the possibility of adverse events. New anticoagulants are being developed that directly target a single coagulation factor. The agents have improved pharmacokinetics and pharmacodynamics and may not need coagulation monitoring. In addition, many are available orally. Agents that target factor Xa or factor IIa are the most advanced in development and of greatest interest. Fondaparinux and idraparinux are parenteral, specific, indirect, factor Xa inhibitors that have a mechanism of action similar to that of heparin. Idraparinux has a prolonged half-life and is dosed once weekly. Razaxaban is a small-molecule, oral, direct FXa inhibitor with demonstrated efficacy in orthopedic surgery for primary prevention of venous thromboembolism. Other oral Xa inhibitors are entering clinical trials. Ximelagatran is an oral factor IIa or thrombin inhibitor with documented efficacy for primary prevention of venous thromboembolism in orthopedic surgery, for the acute and chronic treatment of deep venous thrombosis and stroke prevention in atrial fibrillation. Other oral IIa inhibitors are entering clinical trials. Many of these agents will have a profound effect on the treatment of venous thromboembolism potentially resulting in reduced costs, improved patient satisfaction with treatment, and greater use of selected indications.
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PMID:New anticoagulants and their potential impact on the treatment of thromboembolic disease. 1534 3


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