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

Argatroban, a direct thrombin inhibitor, effectively inhibits free and clot-bound thrombin without the need of a cofactor and exerts dose-dependent anticoagulant effects that are rapidly active and rapidly reversible (elimination half-life: 39-51 min). Argatroban provides predictable parenteral anticoagulation and is well tolerated with an acceptably low bleeding risk in a variety of clinical settings, including heparin-induced thrombocytopenia, acute ischemic stroke, percutaneous coronary intervention and hemodialysis. This review will discuss the clinical pharmacology and utility of argatroban; in particular, clinical trial experiences will be discussed in patients with, or at risk of, heparin-induced thrombocytopenia (where heparins must be avoided) including those requiring hemodialysis or percutaneous coronary intervention, and in patients with acute ischemic stroke (where heparins are not generally recommended).
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PMID:Alternative parenteral anticoagulation with argatroban, a direct thrombin inhibitor. 1572 73

Argatroban, a synthetic peptidomimetic antithrombin agent, is the first clinical anticoagulant solely to target thrombin. For some time, this drug has been used in Japan for the management of thromboembolic disorders. Recently, it has been approved in Japan for use in thrombotic and ischaemic stroke. Despite a large number of preclinical studies on the pharmacology of this agent, clinical trials in Europe and North America were only initiated in 1996. Argatroban produces anticoagulant effects comparable to therapeutic heparinisation at concentrations of approximately 1 microg/ml. At concentrations of 5-10 microg/ml, this agent produces adequate anticoagulation for inteventional cardiovascular procedures and prolongs the activated clotting time (ACT) to 400-600 s. The predictable anticoagulant effect of this agent is relatively short lasting, and may not warrant pharmacologic neutralisation in the majority of patients. However, patients with hepatic dysfunction may need some means of neutralisation. Unlike heparin, this drug produces its anticoagulant effects by direct inhibition of thrombin and thrombin-mediated processes. This agent is not influenced by endogenous factors such as platelet factor 4 and other proteins which bind heparin. Argatroban's use does not lead to the formation of antiplatelet antibodies. Thus, this drug is useful in the management of heparin induced thrombocytopenic (HIT) patients. Although argatroban was initially developed for the management of deep vein thrombosis (DVT), based on its pharmacologic properties, it can be developed for safer anticoagulation in such indications as acute coronary syndromes, as an adjunct to thrombolytics, thrombotic and ischaemic stroke and inflammatory diseases resulting in thrombotic complications.
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PMID:Pharmacology of argatroban. 1599 20

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

Unfractionated heparin has historically been used as the anticoagulant of choice in the management of a number of thrombotic diseases. Recognition of the limitations of heparin has led to the development of a newer class of anticoagulants, the direct thrombin inhibitors. Argatroban is a synthetic small molecule that selectively inhibits thrombin at its active site. In preclinical studies, argatroban has been shown to be more effective than heparin in preventing arterial thrombosis and in promoting vessel patency in conjunction with thrombolysis in a number of animal models. In clinical trials, argatroban has been shown to be as effective as heparin in the management of ST-segment elevation myocardial infarction in conjunction with thrombolysis. It has been shown to be an effective anticoagulant in patients undergoing percutaneous coronary interventions. In patients with heparin-induced thrombocytopenia and heparin-induced thrombocytopenia complicated by thrombosis, argatroban significantly decreases the risk of thrombotic events. Small studies have demonstrated a potential role for its use in ischemic stroke and hemodialysis. Additional studies are warranted to confirm argatroban's efficacy in a wide variety of clinical settings.
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PMID:Argatroban: update. 1678 Dec 11

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

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

Heparin induced thrombocytopenia (HIT) is a serious and life endangering complication of heparin therapy. It usually occurs after 5-14 days of continuous heparin therapy. It is immune mediated. Heparin, in the affected individual binds with platelet factor 4 (PF-4) and forms a highly antigenic Heparin PF-4 complex which leads to the generation of specific IgG Heparin PF4 antibodies (also called HIT antibodies). HIT antibodies may activate the platelets via Fcy receptor causing the release of highly coagulable micro particles which promote thrombosis--both venous and arterial. However, all patients with HIT antibodies do not progress to HIT with thrombosis (HITT). HIT can present as asymptomatic thrombocytopenia. It can also present with alarming features of venous and/or arterial thromboembolism, for example, pulmonary embolism from deep vein thrombosis (DVT), limb gangrene warranting amputation, cerebrovascular attack (CVA) or myocardial infarction (MI). Rare manifestation of HIT includes necrotizing skin lesion, acute anaphylactoid reaction following IV heparin bolus and acute adrenal apoplexy due to massive adrenal vein thrombosis. The diagnosis is based upon the combination of unexplained thrombocytopenia, demonstration of HIT antibodies, clinical profile and outcome of the case following withdrawal of heparin and administration of non-heparin anticoagulant like Lepirudin, Argatroban or Danaparoid. The choice of alternative anticoagulant depends upon the availability, cost, monitoring facilities and administrative guidelines.
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PMID:Heparin induced thrombocytopenia. 1905 9

Argatroban is a synthetic direct thrombin inhibitor with a relative short elimination half-life of 45 minutes and elimination which is predominantly performed via hepatic metabolism. Argatroban anticoagulation has been systematically studied in patients exhibiting the heparin-induced thrombocytopenia (HIT)/thrombosis syndrome and demonstrated to be a safe and effective therapy in this indication. Moreover, in smaller studies argatroban has also been assessed in special clinical settings in non-HIT patients. The current review presents the pharmacology of argatroban, data regarding monitoring of the agent, and an overview of the results of the major clinical trials assessing argatroban anticoagulation in HIT patients. Additionally, data from clinical trials with argatroban use outside HIT, in more special indications such as in percutaneous coronary intervention, stroke, renal replacement therapy, and intensive care medicine, are reviewed.
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PMID:The direct thrombin inhibitor argatroban: a review of its use in patients with and without HIT. 1970 20

The small molecule, arginomimetic drug argatroban is the first synthetic direct antithrombin to be approved for clinical use. Argatroban reversibly binds to and inhibits both soluble and clot-bound thrombin. In contrast to other direct thrombin inhibitors, argatroban upregulates nitric oxide, enhancing its antithrombotic effect, does not generate antibodies, is not susceptible to degradation by proteases and is hepatically cleared. It has a predictable anticoagulant effect. Argatroban has proven efficacy and safety for prophylaxis and treatment of patients with thrombosis associated with heparin-induced thrombocytopenia (HIT), and for percutaneous coronary intervention in HIT and non-HIT patients. Pilot studies suggest that further investigations to establish the use of argatroban in ischemic stroke, acute coronary syndrome, hemodialysis, blood oxygenation, off-pump cardiac surgery and other clinical indications are warranted.
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PMID:Update on the clinical applications of argatroban. 1980 76

Argatroban is a synthetic, small-molecule direct thrombin inhibitor that is approved in the USA, the EU and Japan for prophylaxis or treatment of thrombosis in patients with heparin-induced thrombocytopenia (HIT), and for anticoagulation of HIT patients undergoing PCI. Argatroban binds reversibly to, and inhibits both soluble and clot-bound thrombin. Argatroban does not generate antibodies, is not susceptible to degradation by proteases and is cleared hepatically. It has a predictable anticoagulant effect and there is a good correlation between dose, plasma concentration and pharmacodynamic effect. Initial clinical studies suggest that further investigations to establish the use of argatroban in ischemic stroke, acute coronary syndrome, hemodialysis, blood oxygenation, off-pump cardiac surgery and other clinical indications are warranted.
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PMID:Pharmacology of argatroban. 2108 69


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