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

Anticoagulation with oral vitamin K antagonists (VKA) is the mainstay of the treatment of venous and/or arterial thromboembolism in patients with antiphospholipid syndrome (APS), although the optimal intensity of anticoagulation remains controversial. The limitations of existing anticoagulants have driven a search for novel agents. Dabigatran etexilate (Pradaxa), a direct thrombin inhibitor (DTI), and rivaroxaban (Xarelto), the first in a new class of drugs, the oral direct factor Xa (FXa) inhibitors, are both fixed-dose orally administered agents. They are now licensed in the UK and Europe for the prevention of venous thromboembolism (VTE) in adult patients undergoing elective total hip replacement (THR) or total knee replacement (TKR). Prospective randomized clinical trials suggest that these agents, and also apixaban, a further oral direct anti-Xa inhibitor, may have potential in other areas including the treatment of acute VTE, prevention of stroke or systemic embolism in patients with atrial fibrillation (AF) and acute coronary syndromes. Here, we summarize current indications for these agents and address the potential for their use in patients with thrombotic APS.
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PMID:Antithrombotic treatment failures in antiphospholipid syndrome: the new anticoagulants? 2035 92

Recent data suggest that patients with a malignancy have a seven-fold increased risk for venous thromboembolism (VTE) compared with those without cancer, suggesting that these patients may benefit from thromboprophylaxis. Mechanisms for the prevention of thromboembolism can be divided into two broad categories: mechanical and pharmacological. Although generally used in combination with pharmacotherapy, little evidence exists for the efficacy of mechanical modalities either in the broader population of patients at risk for VTE or for patients with cancer specifically. A recent study using graduated compression stockings (GCS) for thromboprophylaxis showed no support for the use of stockings in acute stroke patients. Established pharmacological modalities, including warfarin, unfractionated heparin (UFH), low-molecular-weight heparin (LMWH), and the factor Xa inhibitor fondaparinux, have been shown to reduce risk for VTE in general medical and surgical populations. In medical cancer patients, only limited data are available for the efficacy of thromboprophylaxis. In contrast, considerable evidence indicates that thromboprophylaxis is warranted in patients undergoing cancer surgery. The most recent evidence suggests that catheter-related thrombosis is not prevented by current pharmacological modalities. On 22 May 2009, a group of clinicians based in the United Kingdom (UK) met in London, UK, to evaluate recent data on cancer thrombosis. This article (the second of four) briefly reviews key data on the prevention of VTE in medical and surgical oncology patients, providing context for a brief transcript of the surrounding discussion and a consensus statement, developed by meeting attendees, on the implications of this information for UK clinical practice.
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PMID:Primary prevention of venous thromboembolism in medical and surgical oncology patients. 2038 44

Atrial fibrillation (AF) is the most common cardiac arrhythmia in the elderly, affecting 1 in 20 adults over the age of 70 years. Stroke is a major yet highly preventable complication of AF, and the strokes related to AF often are disabling and fatal. Warfarin is the treatment of choice in high-risk patients with AF, and its superior efficacy over aspirin for preventing stroke in these patients is widely recognized. However, several eligible patients with AF are not being treated with warfarin or are being treated inadequately, largely because of concerns regarding the attendant strict monitoring, drug interactions, and risk of major bleeding. As such, alternative antithrombotic therapies that can rival or exceed the efficacy of warfarin, yet compare favorably with its administration and side effect profile, are being sought. One such strategy, the use of a combination antiplatelet regimen, for stroke prevention in high-risk patients with nonvalvular AF was investigated recently in two clinical trials. This article reviews the role of combination antiplatelet regimens in stroke prevention for patients with AF. Other therapies discussed include oral anticoagulation, single antiplatelet therapies, oral anticoagulation plus antiplatelet treatment, direct thrombin inhibitors, and factor Xa inhibitors.
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PMID:Update on antithrombotic therapy for stroke prevention in atrial fibrillation. 2046 Nov 16

The development of hemostasis research at Karolinska Institutet is described, focusing first on the initial findings of the fibrinogen structure and the hereditary bleeding disorders, hemophilia A and von Willebrand's disease. Basic research has focused on new biomarkers for cardiovascular/thromboembolic disorders, such as myocardial infarction and stroke, including preeclampsia and diabetes, with studies on the importance of decreased fibrinolysis in these disorders. Since long, the structure of the fibrin network has been evaluated, and recently the influence of aspirin and new thrombin and factor Xa inhibitors has been investigated. Research on the contact pathway of coagulation has also started at the Unit.
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PMID:Molecular aspects in clinical hemostasis research at Karolinska Institutet. 2049 25

Currently, there are several lines of evidence supporting the interplay between coagulation and inflammation in the propagation of various disease processes, including venous thromboembolism (VTE) and inflammatory diseases. Major advances in the development of oral anticoagulants have resulted in considerable progress toward the goal of safe and effective oral anticoagulants that do not require frequent monitoring or dose adjustment and have minimal food/drug interactions. Indirect inhibitors such as low-molecular-weight heparin (LMWH) and the pentasaccharide fondaparinux represent improvements over traditional drugs such as unfractionated heparin for acute treatment of VTE, constituting a more targeted anticoagulant approach with predictable pharmacokinetic profiles and no requirement for monitoring. Vitamin K antagonist, with its inherent limitations in terms of multiple food and drug interactions and frequent need for monitoring, remains the only oral anticoagulant approved for long-term secondary thromboprophylaxis in VTE. The oral-direct thrombin inhibitor ximelagatran was withdrawn from the world market due to safety concerns. Newer anticoagulant drugs such as parenteral pentasaccharides (idraparinux, SSR126517E), novel oral-direct thrombin inhibitors (dabigatran), oral-direct factor Xa inhibitors (rivaroxaban, apixaban, YM-150, DU-176b), and tissue factor/factor VIIa complex inhibitors have been "tailor-made" to target specific procoagulant complexes and have the potential to greatly expand oral antithrombotic targets for both acute and long-term treatment of VTE, acute coronary syndromes, and for the prevention of stroke in atrial fibrillation patients.
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PMID:Novel anticoagulant therapy: principle and practice. 2061 17

Rivaroxaban is a small-molecule, direct factor Xa inhibitor that is under investigation for the prevention and treatment of venous and arterial thrombosis. To date, oral anticoagulants have been limited largely to vitamin K antagonists. Despite their remarkable benefits, vitamin K antagonists are limited by their narrow therapeutic window, the existence of multiple food and drug interactions, and the need for frequent monitoring and dose-adjustment. Rivaroxaban represents a potentially attractive alternative to warfarin, as it could enable simplified once-daily dosing, requires no therapeutic monitoring, and has a lower potential for drug interactions. At present, the safety and efficacy of rivaroxaban for the prophylaxis and treatment of venous thromboembolism has been evaluated in phase-II and phase-III trials involving over 24,000 patients. Rivaroxaban is also being evaluated for the treatment of pulmonary embolism, secondary prevention after acute coronary syndromes, and the prevention of stroke and non-central nervous system embolism in patients with non-valvular atrial fibrillation. The need for new oral anticoagulants, the development and pharmacology of rivaroxaban, results of completed studies of rivaroxaban, and details of ongoing phase-II and phase-III trials with rivaroxaban are the subjects of this chapter.
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PMID:Oral direct factor Xa inhibitors, with special emphasis on rivaroxaban. 2061 18

Atrial fibrillation (AF) is the most commonly occurring arrhythmia, and is a condition of both significant clinical and economic importance. An antithrombotic agent is considered mandatory as part of the management in most patients with AF. It has been conclusively demonstrated that long-term anticoagulation therapy can significantly reduce the risk of stroke in patients with nonvalvular AF. While vitamin K antagonists (VKAs) such as warfarin are highly effective, they possess numerous limitations that curtail their use, or make their use challenging for clinicians and patients. A new generation of anticoagulants are being investigated in phase III clinical trials in patients with AF. One or more of these agents have the potential to either replace or act as alternatives to VKA therapy in AF. This group includes the direct thrombin inhibitor, dabigatran, the direct factor Xa inhibitors rivaroxaban, apixaban, and edoxaban, and finally, the vitamin K analogue, tecarfarin. Additional agents are being developed in phase I or II clinical trials. The direct thrombin and factor Xa inhibitors are generally small, synthetic molecules with predictable pharmacokinetics, a predictable pharmacodynamic effect, few drug interactions and do not require routine therapeutic drug monitoring. These new anticoagulants may well represent a new era in anticoagulation. However, they do possess their own limitations and will present new challenges for clinicians.
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PMID:New antithrombotics for atrial fibrillation. 2064 85

The decline in stroke incidence and mortality in the U.S. over the past 20 years is reaching a plateau, and the number of strokes may actually start to increase as the population ages. However, recent clinical trials have demonstrated that there are numerous opportunities to improve stroke prevention strategies and also opportunities to effectively intervene in and treat acute strokes. For patients with diabetes and for those with prior strokes or transient ischemic attacks, it has become evident that aggressive low-density lipoprotein lowering with statin medications will decrease the risk for total and fatal strokes. Optimal anticoagulation and antiplatelet therapy for primary and secondary stroke prevention in atrial fibrillation is being carefully defined. With numerous novel factor Xa and direct thrombin inhibitor drugs completing phase III clinical trials, it is likely that additional oral anticoagulant drugs will be clinically available for stroke prevention soon. Additionally, a major clinical trial is nearing completion that may resolve the role of carotid stenting and carotid endarterectomy in primary and secondary stroke prevention. There are recent notable advances in the acute treatment of stroke. It is likely that the time window for thrombolysis for appropriate patients with strokes will be increased from 3 to 4.5 h, permitting the inclusion of more patients in this treatment approach. There is ongoing investigation of intra-arterial thrombolysis and of acute intra-arterial thrombus extraction for treatment of selected patients with strokes. Unlike the progress in treatment of ischemic strokes, treatment of hemorrhagic stroke is progressing more slowly.
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PMID:Stroke prevention and treatment. 2072 98

Many years of practical use and intensive scientific research have allowed vitamin K antagonists to become a cornerstone of treatment of internal diseases. Nevertheless, limitations in pharmacokinetics and -dynamics of vitamin K antagonists and the availability of new drugs in regard to a targeted anticoagulation therapy ask for a new review of the situation. Proof of effectiveness for the perioperative prophylaxis of venous thrombosis after hip and knee replacement has already been achieved for the direct thrombin inhibitor dabigatran etexilate as well as for the factor Xa inhibitors rivaroxaban und apixaban compared to low molecular weight heparins. These new drugs are now also investigated in patients with internal diseases. For the long-term application (6 or 12 months) concerning the treatment of venous thrombosis and/or stroke prophylaxis in patients with atrial fibrillation data is already available for the direct thrombin inhibitor dabigatran etexilate. Depending on its dosage its effectiveness in comparison with vitamin K antagonists is equal or even better without disadvantages in safety. However, vitamin K antagonists will remain the standard oral anticoagulation until open questions regarding e.g. insufficient therapy adherence (with termination rates up to 20%) or problems with drug interactions of the new competitive products have been completely answered.
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PMID:[New oral anticoagulants: better than vitamin K antagonists?]. 2080 75

Prothrombin fragment 1+2 (F1+2), which comes from in vivo cleavage of prothrombin by factor Xa, is considered to be useful for diagnosis of thrombosis. Recognition of the central role of thrombosis in the pathogenesis ofcardiovascular disease has prompted growing interest in the association o F1+2 with cardiovascular clinical syndromes. Increased F1+2 levels have reported in venous thromboembolism, inflammation, cancer, sepsis, acute coronary syndromes, stroke, peripheral arterial disease, atrial fibrillation and during the postoperative period. However, a clear relationship with the appearance of thrombosis has not always been consistently demonstrated. Besides its potential prognostic and diagnostic value, it could also be usefu in assessing the impact of various therapies. However, it should be kept in mind that measurement of hemostasis activation markers has several important biological and methodological disadvantages. Activation markers reflect the presence of thrombosis in any vascular bed, so they are not specific. Furthermore, elevations occur not only in the presence of overt thrombosis but also during the hypercoagulable state. The cutoff level to be used for the definition of elevations is still largely unknown due to the use of different analytical methods, none of which have been standardized until know. Finally, the prognostic value of F1+2 and other markers of coagulation activation remains to be fully defined in future studies.
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PMID:Prothrombin fragments in cardiovascular disease. 2085 16


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