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

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia. The prevalence of AF increases sharply in old age (prevalence approximately 10% among persons 80 years of age and older). The expected risk for ischemic stroke is increased five-fold by the presence of AF, primarily as a result of cardiogenic embolism. Multiple large-scale, randomized trials have been completed or are still underway to find optimal, efficacious, and relatively safe ways to reduce the risk of ischemic stroke and other systemic thromboembolic events related to AF. Antithrombotic strategies are accompanied by serious bleeding complications that threaten patients in need of medical stroke prevention. Treatment regimens for preventing thromboembolism in AF patients range from vitamin K antagonists such as warfarin or coumadins, antiplatelet drugs like aspirin or clopidogrel, to newly developed orally available antithrombotics like the direct thrombin inhibitor dabigatran, or the Factor Xa-inhibitor rivaroxaban. The available anticoagulant and antiplatelet drugs have different advantages and disadvantages. This review attempts to delineate the specific role of clopidogrel in patients with AF and at risk of stroke, taking into consideration new and ongoing trials in this important field of medical practice.
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PMID:Modern role for clopidogrel in management of atrial fibrillation and stroke reduction. 2023 84

Atrial fibrillation causes a significant burden on patients and the health care system. The main goals of atrial fibrillation therapy are to improve symptoms and reduce morbidity. There have been significant recent developments in both stoke prophylaxis and rhythm/rate control. The results of the ACTIVE W study emphasize the importance of effective oral anticoagulant therapy in patients with moderate-to-high risk for stroke. The RE-LY study showed superiority of dabigatran, an oral direct thrombin inhibitor, over warfarin in the prevention of stroke, or systemic embolism. Dronedarone, a new antiarrhythmic drug with multiple class effects, has been recently approved by the US Food and Drug Administration for the treatment of atrial fibrillation. Dronedarone has moderate rhythm and rate control efficacy; however, dronedarone significantly reduced cardiovascular hospitalization, cardiovascular death, and stroke in the large ATHENA trial. There is also an important shift in the paradigm of the goals of atrial fibrillation therapy. Instead of focusing solely on the electrocardiographic outcomes of treatment and considering "rhythm versus rate control," one needs to consider "symptom control" as well as patient well-being. This review will suggest that patient based outcomes rather than ECG-based outcomes should be the primary goals of treatment. Original reports and reviews on specific topics were identified through Medline. Randomized controlled trials were selected as the primary source of information. Analysis included critical review of the evidence available to date.
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PMID:New approaches to atrial fibrillation management: treat the patient, not the ECG. 2034 95

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

Dabigatran etexilate was recently approved by the Therapeutic Goods Administration for thromboprophylactic use in adults undergoing elective total hip or knee replacement. Dabigatran etexilate is the prodrug of the active moiety dabigatran, an orally active agent that could replace enoxaparin in some clinical indications. Dabigatran is a direct thrombin inhibitor; it has stable, predictable pharmacokinetics and does not require routine monitoring. Pooled efficacy data from large-scale phase III clinical trials of dabigatran use in orthopaedic thromboprophylaxis have shown non-inferiority to enoxaparin, with total venous thromboembolism results of 3.8% for dabigatran etexilate 150 mg and 3.0% for dabigatran etexilate 220 mg, compared with 3.3% for enoxaparin. Pooled safety results for dabigatran are similar to those for enoxaparin, with major bleeding rates of 1.1% for dabigatran etexilate 150 mg and 1.4% for dabigatran etexilate 220 mg, compared with 1.4% for enoxaparin. Dabigatran failed to demonstrate non-inferiority compared with enoxaparin 30 mg twice daily for orthopaedic thromboprophylaxis. Issues relating to the use of dabigatran include its lack of antidote, limited application in renal disease, and interaction with drugs such as amiodarone and verapamil. Several trials investigating the use of dabigatran for other indications, such as stroke prevention in atrial fibrillation and acute coronary syndromes, are underway. Given its safety profile, efficacy, oral bioavailability and stable pharmacokinetic properties, dabigatran may be a viable alternative to enoxaparin for thromboprophylaxis in orthopaedic surgery.
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PMID:Dabigatran etexilate: a new thrombin inhibitor. 2036 91

Atrial fibrillation is the most common cardiac arrhythmia responsible for one third of the hospitalizations because of cardiac rhythm disturbances. Atrial fibrillation leads to stroke, heart failure, and other causes of mortality. Warfarin, a vitamin K antagonist, is the first-line agent for the prophylaxis of stroke in patients with atrial fibrillation. Limitations associated with warfarin have led to development of new anticoagulants targeting different sites in the coagulation cascade. A direct thrombin inhibitor, dabigatran, has been evaluated in clinical studies for prophylaxis in atrial fibrillation. Factor Xa inhibitors, direct as well as indirect inhibitors, are in various stages of development for their antithrombotic effect. This article reviews the studies done on these novel anticoagulants and their prophylactic potential for the prevention of stroke in atrial fibrillation.
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PMID:Newer anticoagulants as an alternate to warfarin in atrial fibrillation: a changing paradigm. 2046 Sep 86

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

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

Dabigatran is a highly selective, reversible, and potent thrombin inhibitor and is orally available as the prodrug, dabigatran etexilate. It has shown antithrombotic efficacy in animal models of thrombosis, with a rapid onset of action and predictable pharmacodynamic response. Peak plasma concentrations of dabigatran occur 1 to 2 hours after ingestion of the prodrug. The terminal half-life of dabigatran is 12 to 14 hours in elderly volunteers. Dabigatran is not metabolized by cytochrome P450 isoenzymes and does not interact with food. Dabigatran has a low potential for drug-drug interactions and is predominantly renally excreted. Dabigatran etexilate as chronic therapy effectively prevents the recurrence of venous thromboembolism and cardioembolic stroke. For the first time, it has been demonstrated clinically that there may be an effective and safe alternative to warfarin.
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PMID:Dabigatran: an oral novel potent reversible nonpeptide inhibitor of thrombin. 2067 Dec 33

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


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