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

Heparin remains the most commonly used anticoagulant in the treatment of patients with acute vascular syndromes, including myocardial infarction, unstable angina and ischaemic stroke. However, heparin therapy is not always associated with a significant improvement of clinical outcomes, is linked with enhanced bleeding risk and can occasionally provoke the development of heparin-induced thrombocytopaenia, the most devastating complication of conventional therapy with unfractioned heparin. Understanding the key role of thrombin in clot formation and platelet activation has stimulated the development of a new class of drugs - direct thrombin inhibitors. The direct thrombin inhibitor argatroban has been known for decades. Similar to the unfractioned heparin, argatroban requires intravenous administration and activated partial prothrombin time-dependent dose adjustment; however, this pharmacological agent has a relatively short half-life that broadens its safety margins, as well as its low antigenic potential due to the small molecular weight of the compound. The efficacy of argatroban has been demonstrated among patients with acute coronary syndromes and stroke. However, this drug is currently approved by the FDA only for the treatment of patients with heparin-induced thrombocytopaenia. Indeed, in such patients, argatroban significantly improves clinical outcomes, and is associated with reduced mortality. Further clinical studies are needed to present more clinical evidence necessary to broad the indication spectrum of this agent.
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PMID:Argatroban, a direct thrombin inhibitor for heparin-induced thrombocytopaenia: present and future perspectives. 1637 Sep 25

A decision-tree analysis was used to estimate the average cost per patient using the direct thrombin inhibitor argatroban for early treatment (<48 hours after thrombocytopenia onset) compared with delayed treatment (> or =48 hours after thrombocytopenia onset) of immune-mediated heparin-induced thrombocytopenia (HIT) with or without thrombosis. Clinical probability data used to populate the model were obtained from argatroban clinical trials and from published clinical literature. Resource utilization data and cost data were also obtained from available literature, the 2003 Physician's Fee Reference, the Healthcare Cost and Utilization Project 2000, the 2003 Drug Topics RedBook, and a modified Delphi panel. The total per-patient cost included hospital days, diagnostic tests, heparin, argatroban, major hemorrhagic events, and patient outcomes (ie, amputation, new thrombosis, stroke, or death), multiplied by the probability of each event. The incremental cost-effectiveness ratio was calculated by dividing the incremental cost between patients with and without argatroban treatment by the incremental effectiveness, or the cost per new thrombosis event avoided. The mean cost per HIT patient without thrombosis who did not receive argatroban was $38,046. The mean cost decreased by 6.85% for patients who were treated earlier with argatroban therapy (average cost, $35,441), representing a $2605 saving per patient compared with those not treated with argatroban. For those receiving delayed argatroban therapy, the mean cost increased by $9024 per patient compared with those receiving early treatment with argatroban. The mean cost for HIT patients with thrombosis who did not receive argatroban was $48,101, which was 9.0% higher than for those receiving early argatroban therapy, representing a $3957 savings per patient. For HIT with thrombosis, mean costs increased by 18.2% in patients whose argatroban was delayed, representing a cost increase of $8020 per patient compared with early treatment (mean cost $44,144 for early treatment and $52,164 for delayed treatment). The results of this analysis support the recommendation to initiate early argatroban treatment upon suspicion of HIT to reduce the thrombotic consequences of HIT and associated healthcare costs. Argatroban therapy should not be delayed pending the results of HIT diagnostic tests.
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PMID:The cost-effectiveness of argatroban treatment in heparin-induced thrombocytopenia: the effect of early versus delayed treatment. 1637 60

Traditional anticoagulant drugs, including unfractionated heparin and warfarin, have several limitations. A new strategy for the design of new antithrombotic drugs is based on selective inhibition of a specific coagulation factor. These include direct thrombin inhibitors and factor Xa inhibitors. Two parenteral direct thrombin inhibitors, lepirudin and argatroban, have FDA approval for the management of heparin-induced thrombocytopenia. Ximelagatran, an oral prodrug of the direct thrombin inhibitor melagatran, has shown efficacy in the prevention and treatment of venous thromboembolism as well as stroke prevention in patients with atrial fibrillation. Fondaparinux is a synthetic pentasaccharide, which binds to antithrombin, thereby indirectly selectively inhibiting factor Xa. Fondaparinux has demonstrated its efficacy compared to low-molecular-weight heparin in randomized clinical trials and is FDA approved for the prevention and treatment of venous thromboembolism. A number of oral direct factor Xa inhibitors as well as other oral direct thrombin inhibitors are in clinical development for the prevention and treatment of thrombosis.
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PMID:New anticoagulants: anti IIa vs anti Xa--is one better? 1647 45

Despite the significant advances over the last 50 years with regard to anticoagulant therapy, warfarin remains the definitive standard for the long-term prevention of thromboembolic events in at-risk patients, except those with acute coronary syndromes, in which antiplatelets are preferred. Ximelagatran, a prodrug of melagatran, is an orally administered direct thrombin inhibitor whose therapeutic potential has been investigated in venous thromboembolism, acute coronary syndromes and prevention of stroke in atrial fibrillation. Clinical studies have demonstrated ximelagatran to be comparable in efficacy to the oral vitamin K antagonist warfarin and low molecular weight heparin for prophylaxis of venous thromboembolism, comparable to warfarin for stroke prevention in the setting of atrial fibrillation, and, when combined with aspirin, more effective than aspirin alone at preventing major adverse cardiovascular events in patients with a recent myocardial infarction. Double-blind trials have also revealed the efficacy of ximelagatran in the secondary prevention of venous thromboembolism and shown the agent to be as effective as enoxaparin/warfarin in treating patients with acute deep vein thrombosis. Adverse effects with ximelagatran include elevations in alanine transaminase (ALT), which may require monitoring, and bleeding complications. Bleeding complications appear to be less than or at least comparable to those occurring with standard anticoagulant treatments like warfarin or low molecular weight heparin. In addition to its favorable efficacy and safety profile in comparison with standard anticoagulant therapy, the convenience of its oral, fixed-dose administration without the need for anticoagulation monitoring might help encourage a wider use of appropriate anticoagulation using ximelagatran across the population at risk, reducing the incidence of thromboembolic events.
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PMID:Ximelagatran. 1651 7

The last decade witnessed major advances in the prevention and treatment of venous as well as of arterial thrombosis. Limitations of existing anticoagulants led to the development of novel therapeutic approaches. Ximelagatran is a new direct thrombin inhibitor (DTI) that is given orally, without the need for close monitoring. This compound was tried in the treatment of active venous thromboembolism, and the results were encouraging. Randomized trials suggest that ximelagatran is not inferior to warfarin in the prevention of stroke in patients with nonvalvular atrial fibrillation. Multiple controlled, prospective trials compared ximelagatran with low molecular weight heparin or warfarin in prevention of venous thromboembolism in patients undergoing major orthopedic procedures. The results of these clinical trials are reviewed in this article. Because of certain safety concerns (increased liver enzymes, potential hepatonecrosis, and increased coronary events) ximelagatran has not yet been approved by the FDA. Additional studies may be required to address these concerns. Ximelagatran has been approved, however, by the European regulatory authorities for short-term thromboprophylaxis. The success of ximelagatran or other oral antithrombin agents would provide significant proof of the concept for the long-term use of oral antithrombins in the prevention and treatment of both arterial and venous thrombosis.
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PMID:Ximelagatran, the new oral anticoagulant: would warfarin survive the challenge? 1661 32

A 49-year-old Caucasian man with antiphospholipid syndrome who experienced an ischemic stroke required multidisciplinary decisions regarding acute and long-term care. The patient first received warfarin and unfractionated heparin, followed by low-molecular-weight heparin. However, he developed complications from these drugs (warfarin-induced necrosis and heparin-induced thrombocytopenia), resulting in thigh necrosis and multiple additional cerebral and peripheral infarcts. His condition improved after warfarin and the heparins were discontinued, and a direct thrombin inhibitor, argatroban, was given intravenously for acute treatment. Argatroban is the only anticoagulant known to be safe in patients who experience an acute ischemic stroke in the setting of heparin-induced thrombocytopenia. For long-term anticoagulation, fondaparinux, an indirect, selective factor Xa inhibitor, was given subcutaneously. The patient received intravenous dexamethasone, later changed to azathioprine, for immunomodulatory treatment. He had significant improvement in his neurologic deficits without recurrent events over the next 18 months. Management of anticoagulation therapy in patients with antiphospholipid syndrome is complex and challenging, and therapeutic strategies need to be evaluated further.
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PMID:Anticoagulation strategies for treatment of ischemic stroke and antiphospholipid syndrome: case report and review of the literature. 1699 62

Atrial fibrillation is associated with substantial morbidity and mortality. Pooled data from trials comparing antithrombotic treatment with placebo have shown that warfarin reduces the risk of stroke by 62%, and that aspirin alone reduces the risk by 22%. Overall, in high-risk patients, warfarin is superior to aspirin in preventing strokes, with a relative risk reduction of 36%. Ximelagatran, an oral direct thrombin inhibitor, was found to be as efficient as vitamin K antagonist drugs in the prevention of embolic events, but has been recently withdrawn because of abnormal liver function tests. The ACTIVE-W (Atrial Fibrillation Clopidogrel Trial with Irbesartan for Prevention of Vascular Events) study has demonstrated that warfarin is superior to platelet therapy (clopidogrel plus aspirin) in the prevention af embolic events. Idraparinux, a Factor Xa inhibitor, is being evaluated in patients with atrial fibrillation. Angiotensin-converting enzyme inhibitors and angiotensin II receptor-blocking drugs hold promise in atrial fibrillation through cardiac remodelling. Preliminary studies suggest that statins could interfere with the risk of recurrence after electrical cardioversion. Finally, percutaneous methods for the exclusion of left atrial appendage are under investigation in high-risk patients.
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PMID:Optimising stroke prevention in non-valvular atrial fibrillation. 1702 Apr 34

Traditional anticoagulant drugs, including unfractionated heparin and warfarin, have several limitations. New anticoagulants have been developed that target a single coagulation factor and have predictable dose-response relationships. These include direct thrombin inhibitors and factor Xa inhibitors. Two parenteral direct thrombin inhibitors, lepirudin and argatroban, have FDA approval for the management of heparin-induced thrombocytopenia (HIT). Bivalirudin is a parenteral direct thrombin inhibitor that is licensed for patients undergoing percutaneous coronary interventions and for those with HIT who require percutaneous coronary interventions. Ximelagatran, an oral prodrug of the direct thrombin inhibitor melagatran, showed efficacy in the prevention and treatment of venous thromboembolism as well as stroke prevention in patients with atrial fibrillation. However, due to nonhematologic safety concerns, it did not receive FDA approval in the US. Fondaparinux is a synthetic pentasaccharide, which binds to antithrombin, thereby indirectly selectively inhibiting factor Xa. Fondaparinux demonstrated efficacy compared to low-molecular-weight heparin in randomized clinical trials and is FDA approved for the prevention and treatment of venous thromboembolism. The OASIS 5 trial in non-ST-segment elevation acute coronary syndromes recently demonstrated that the fondaparinux dose approved for prophylaxis of deep venous thrombosis is as efficacious with respect to ischemic outcomes as therapeutic doses of enoxaparin; fondaparinux, however, was associated with a substantial reduction in major bleeding at 9 days and mortality at 1 and 6 months. A number of oral direct factor Xa inhibitors as well as other oral direct thrombin inhibitors are in clinical development for the prevention and treatment of thrombosis; the current status of these anticoagulants is reviewed along with the challenges faced in designing pivotal clinical trials of these agents in comparison to existing anticoagulants.
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PMID:New anticoagulants. 1712 98

Nonvalvular atrial fibrillation is the most common cardiac arrhythmia associated with a substantial risk of thromboembolism and stroke. Despite numerous disadvantages that limit its efficacy and safety, warfarin is widely used in the prevention and treatment of thromboembolism related with atrial fibrillation. Ximelagatran, an oral direct thrombin inhibitor has the potential to be an alternative choice in the prevention and therapy of thromboembolism related with atrial fibrillation. Studies compared ximelagatran with warfarin in nonvalvular atrial fibrillation at risk for stroke showed that fixed dose oral ximelagatran is effective as adjusted dose warfarin in stroke prevention. Ximelagatran has numerous advantages over warfarin in clinical practice. Although it seems as a promising option for the prevention and therapy of thromboembolism, its safety and efficacy need to be determined definitely by further clinical trials.
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PMID:[Antithrombotic therapy in atrial fibrillation with ximelagatran: can it be an alternative to warfarin?]. 1751 31

Argatroban, which is a thrombin inhibitor, has an indication as a treatment in the acute phase on atherosclerotic ischemic stroke in Japan. Howeve, in cardioembolic stroke, argatroban is considered to be contraindicated with the side effect of hemorrhage, though there is no clear clinical evidence to show that argatroban increases hemorrhagic compared with heparin. The efficacy of anticoagulant treatment with argatroban on cardioembolic stroke was evaluated retrospectively in this study. We identified 3,113 patients from the Japan Standard Stroke Registry Study who had had a cardioembolic ischemic stroke. We excluded patients with the anti-platelet treatment or the combination therapy of anticoagulation. Our analyses are therefore based on a cohort of 2,529 patients who were treated either with heparin, and argatroban, or with no anti-coagulation treatment. With multivariable regression, hemorrhagic it was shown that hemorrhage was significantly reduced in heparin and argatroban treatments in the patients with mild severity. There was no significant difference in the recurrence of ischemic stroke between the treatments. Both argatroban and heparin showed dramatic improvement compared with the no treatment standard, but only heparin achieved statistical significance for mortality and change in NIHSS score (admission to discharge) in the moderate stroke subgroup [NIHSS 11-22]. Both heparin and argatroban [more so than heparin alone] have a significantly reduced mortality risk. From the present study, it is suggested that argatroban may be useful on cardioembolic stroke, increasing the improvement of recovery of stroke severity without increasing the risk of hemorrhage. Further prospective studies are awaited for evaluating better the efficacy of argatroban on cardioembolic stroke.
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PMID:Efficacy of anti-coagulant treatment with argatroban on cardioembolic stroke. 1741 44


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