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Dabigatran and other oral antithrombotic agents for the prevention of stroke in patients with atrial fibrillation  [cached]
Testai F,Aiyagari V
Research Reports in Clinical Cardiology , 2011,
Abstract: Fernando D Testai, Venkatesh AiyagariSection of Neurological Critical Care and Stroke, Department of Neurology and Rehabilitation, Center for Stroke Research, University of Illinois College of Medicine, Chicago, IL, USAAbstract: Atrial fibrillation (AF) is considered to be one of the most prevalent abnormal heart rhythm disorders and a leading cause of cerebral ischemia. The risk of stroke in AF is associated with vascular risk factors including advancing age, hypertension, congestive heart disease, diabetes mellitus, vascular disease, and prior history of stroke or transient ischemic attack. The classic management of patients with AF at risk of suffering stroke includes the use of warfarin. The use of this medication in clinical practice is, however, limited owing to its narrow therapeutic window, multiple drug and food interactions, prolonged half-life, and the need for periodic anticoagulation monitoring. Recently, newer oral anticoagulants with better pharmacokinetic and pharmacodynamic profiles have been developed and compared to warfarin in phase III trials for the prevention of stroke and systemic embolism in patients with AF. Dabigatran stands out from these studies as a safe and efficacious alternative to warfarin for treating patients with AF at risk of stroke. In this article we review classic and novel approaches for stroke prevention in AF with special emphasis on dabigatran.Keywords: oral anticoagulants, vitamin K antagonists, antiplatelet agents, stroke prevention, atrial fibrillation
Transcatheter occlusion of left atrial appendage for stroke prevention in patients with atrial fibrillation
J.-W. Park,B. Leith?user,F. Jung
Applied Cardiopulmonary Pathophysiology , 2009,
Abstract: Cardiac emboli in patients with atrial fibrillation are one of the major causes of ischemic stroke. Because the vast majority of these cardiac emboli descend from the left atrial appendage (LAA), the therapeutic strategy of percutaneous transcatheter occlusion of the LAA by means of a mechanical implant was a logical consequence. Three different devices have been developed and used in humans: PLAATO, WATCHMAN, and ACP. The PLAATO implant, a "soccer ball" shaped self-expanding nitinol cage has demonstrated stroke prevention capability in small, uncontrolled studies. The WATCHMAN implant, a "half rugby ball" shaped self-expanding nitinol cage, has demonstrated non inferiority compared to warfarin treatment in the randomized, controlled PROTECT AF trial. The ACP implant is also a self-expanding nitinol cage. However, its design is of fundamental difference compared to the other two implants. ACP consists of two parts connected by a short waist, which are an "icehockey puck" shaped body for the implant fixation in the appendage wall, and a flexible disc for sealing the appendage ostium. Due to the very flexible connecting waist between the two parts, ACP implant adapts itself to the LAA, which appears in significant individual structural variabilities. The currently unpublished initial experience with ACP in Europe is encouraging. Transcatheter occlusion of the LAA offers an appealing way to reduce the incidence of cardioembolic stroke in patients with atrial fibrillation. However, the concerns about procedural safety and the need for long-term follow up should be addressed before this potentially important technology is deployed widely.
Dabigatran and other oral antithrombotic agents for the prevention of stroke in patients with atrial fibrillation
Testai F, Aiyagari V
Research Reports in Clinical Cardiology , 2011, DOI: http://dx.doi.org/10.2147/RRCC.S15248
Abstract: bigatran and other oral antithrombotic agents for the prevention of stroke in patients with atrial fibrillation Review (3452) Total Article Views Authors: Testai F, Aiyagari V Published Date June 2011 Volume 2011:2 Pages 71 - 81 DOI: http://dx.doi.org/10.2147/RRCC.S15248 Fernando D Testai, Venkatesh Aiyagari Section of Neurological Critical Care and Stroke, Department of Neurology and Rehabilitation, Center for Stroke Research, University of Illinois College of Medicine, Chicago, IL, USA Abstract: Atrial fibrillation (AF) is considered to be one of the most prevalent abnormal heart rhythm disorders and a leading cause of cerebral ischemia. The risk of stroke in AF is associated with vascular risk factors including advancing age, hypertension, congestive heart disease, diabetes mellitus, vascular disease, and prior history of stroke or transient ischemic attack. The classic management of patients with AF at risk of suffering stroke includes the use of warfarin. The use of this medication in clinical practice is, however, limited owing to its narrow therapeutic window, multiple drug and food interactions, prolonged half-life, and the need for periodic anticoagulation monitoring. Recently, newer oral anticoagulants with better pharmacokinetic and pharmacodynamic profiles have been developed and compared to warfarin in phase III trials for the prevention of stroke and systemic embolism in patients with AF. Dabigatran stands out from these studies as a safe and efficacious alternative to warfarin for treating patients with AF at risk of stroke. In this article we review classic and novel approaches for stroke prevention in AF with special emphasis on dabigatran.
Oral anticoagulation for prevention of cardioembolic stroke in patients with atrial fibrillation: Focussing the elderly  [PDF]
B. Leith?user,F. Jung,J.-W. Park
Applied Cardiopulmonary Pathophysiology , 2009,
Abstract: Anticoagulation therapy for thromboembolism prophylaxis in patients with atrial fibrillation (AF) is based on quality information derived from numerous randomized controlled trials but continues to be a conundrum for many physicians. Age is the most cited argument to withhold anticoagulation. Ironically, because of their higher risk of stroke, the net benefit of antithrombotic therapy may be greater in octogenarians than in younger patients. Indeed, given the risk of major bleeding there is reason to be skeptical about net benefit when warfarin is used in some elderly patients with AF. This summary reviews the risks of cardioembolic stroke and bleeding in patients with atrial fibrillation with and without oral anticoagulation and spotlights the problematic nature of anticoagulation underuse in the elderly.
Dabigatran for Stroke Prevention in Nonvalvular Atrial Fibrillation: Answers to Challenging “Real-World” Questions  [PDF]
Jorge Ferreira,Daniel Ferreira,Miguel Viana-Baptista,Paulo Bettencourt,Rui Cernadas,Francisco Crespo
Thrombosis , 2012, DOI: 10.1155/2012/867121
Abstract: Dabigatran etexilate is a novel, oral, reversible, direct thrombin inhibitor that constitutes a major breakthrough for stroke prevention in patients with nonvalvular atrial fibrillation (AF). Dabigatran was the first new oral anticoagulant approved in Europe and became available in Portugal, for stroke prevention in nonvalvular AF, earlier than in most European countries. This paper is the joint effort of a panel of experts from different specialties and provides information on the use of dabigatran, in anticipation of the challenges that will come with increased usage.
Left Atrial Appendage Closure for Stroke Prevention in Patients with Atrial Fibrillation and Hereditary Hemorrhagic Telangiectasia  [PDF]
Sebastiaan Velthuis,Martin J. Swaans,Johannes J. Mager,Benno J. W. M. Rensing,Lucas V. A. Boersma,Martijn C. Post
Case Reports in Cardiology , 2012, DOI: 10.1155/2012/646505
Abstract: Atrial fibrillation (AF) is the most common cardiac arrhythmia, affecting millions of individuals worldwide, and a major risk factor for disabling cerebral embolic stroke. Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant inherited disorder, characterized by vascular abnormalities with high-bleeding tendency and therefore intolerance for oral anticoagulation. We report a case of percutaneous closure of the left atrial appendage, which might be a good alternative strategy instead of chronic oral anticoagulation to protect patients with high-risk AF and HHT from cerebral embolic strokes. 1. Introduction Atrial fibrillation (AF) is the most common cardiac arrhythmia and a major risk factor for cerebral embolic stroke. Although oral anticoagulation (OAC) is highly effective in stroke prevention, a substantial number of patients is unable to sustain chronic OAC because of high-bleeding risks. Among these are patients with hereditary hemorrhagic telangiectasia (HHT), who frequently encounter inconvenient epistaxis, gastrointestinal bleedings, or life-threatening bleedings from cerebral or pulmonary arteriovenous malformations. Since most thromboembolic complications in patients with AF arise from the left atrial appendage (LAA), a percutaneous transcatheter LAA closure device was recently developed. This is the first paper about the feasibility of percutaneous LAA closure in patients with high-risk AF and HHT, which can be a promising strategy to protect these patients against embolic stroke, while avoiding the need for long-term OAC. 2. Case Presentation We present a 79-year-old man who had been previously diagnosed with HHT, based on the clinical Cura?ao criteria [1]; his family history revealed numerous first-degree relatives with HHT, physical examination demonstrated several telangiectasia on hands, face, lips, and ears, and he suffered from recurrent epistaxis. DNA analysis confirmed the clinical diagnosis with an ALK-1 gene mutation on chromosome 12. Visceral AVMs in the brain, lungs, liver, or gastro-intestinal tract were excluded with magnetic resonance imaging, echocardiography, computed-tomography, and endoscopy. In addition to HHT, the patient was known with arterial hypertension, a recent cerebral ischemic stroke, and permanent AF. His CHADS2-score of four indicated a high risk of recurrent stroke (8.5%/year) [2]. Since visceral sources of life-threatening hemorrhages were ruled out, a trial of OAC (warfarin) was started. This resulted in extensive epistaxis, requiring repeated blood transfusions despite treatment with iron
An evidence-based review of apixaban and its potential in the prevention of stroke in patients with atrial fibrillation
Deedwania P, Huang GW
Core Evidence , 2012, DOI: http://dx.doi.org/10.2147/CE.S25637
Abstract: n evidence-based review of apixaban and its potential in the prevention of stroke in patients with atrial fibrillation Review (2309) Total Article Views Authors: Deedwania P, Huang GW Published Date July 2012 Volume 2012:7 Pages 49 - 59 DOI: http://dx.doi.org/10.2147/CE.S25637 Received: 22 March 2012 Accepted: 17 April 2012 Published: 09 July 2012 Prakash Deedwania,1 Grace W Huang2 1Chief Cardiology Division, VACCHCS/UCSF, 2Division of Cardiology, UCSF Program, Fresno, CA, USA Abstract: Atrial fibrillation (AF) is a common cardiac arrhythmia, especially in the elderly population. It is associated with cardioembolic complications, particularly strokes, resulting in severe functional deficit or death. AF patients are first stratified into low, intermediate, and high risk for thromboembolic events using the CHADS2 and CHA2DS2-VASc score systems. Depending on their risks, patients are treated with either therapeutic anticoagulation with warfarin or acetylsalicylic acid for stroke prevention. Although warfarin is the recommended therapy, it is underutilized clinically due to concern for narrow therapeutic window, drug-to-drug and drug-to-food interactions, and hemorrhagic complications. Newer anticoagulant agents such as dabigatran (a direct thrombin inhibitor) and rivaroxaban (a direct factor Xa inhibitor) have already been approved by US Food and Drug Administration for stroke prevention in patients with nonvalvular atrial fibrillation. Apixaban is the newest oral direct factor Xa inhibitor and it has been extensively studied in the AVERROES and ARISTOTLE trials. Apixaban demonstrated reduced incidence of primary outcome of stroke and bleeding events when compared with warfarin. Apixaban is currently being reviewed by the Food and Drug Administration as a stroke prophylactic agent. In addition, there are several other indirect factor Xa inhibitors and vitamin K antagonists under study presently. Results from these studies will provide us with information about possible alternatives to warfarin.
An evidence-based review of apixaban and its potential in the prevention of stroke in patients with atrial fibrillation  [cached]
Deedwania P,Huang GW
Core Evidence , 2012,
Abstract: Prakash Deedwania,1 Grace W Huang21Chief Cardiology Division, VACCHCS/UCSF, 2Division of Cardiology, UCSF Program, Fresno, CA, USAAbstract: Atrial fibrillation (AF) is a common cardiac arrhythmia, especially in the elderly population. It is associated with cardioembolic complications, particularly strokes, resulting in severe functional deficit or death. AF patients are first stratified into low, intermediate, and high risk for thromboembolic events using the CHADS2 and CHA2DS2-VASc score systems. Depending on their risks, patients are treated with either therapeutic anticoagulation with warfarin or acetylsalicylic acid for stroke prevention. Although warfarin is the recommended therapy, it is underutilized clinically due to concern for narrow therapeutic window, drug-to-drug and drug-to-food interactions, and hemorrhagic complications. Newer anticoagulant agents such as dabigatran (a direct thrombin inhibitor) and rivaroxaban (a direct factor Xa inhibitor) have already been approved by US Food and Drug Administration for stroke prevention in patients with nonvalvular atrial fibrillation. Apixaban is the newest oral direct factor Xa inhibitor and it has been extensively studied in the AVERROES and ARISTOTLE trials. Apixaban demonstrated reduced incidence of primary outcome of stroke and bleeding events when compared with warfarin. Apixaban is currently being reviewed by the Food and Drug Administration as a stroke prophylactic agent. In addition, there are several other indirect factor Xa inhibitors and vitamin K antagonists under study presently. Results from these studies will provide us with information about possible alternatives to warfarin.Keywords: atrial fibrillation, stroke prevention, apixaban
Dabigatran for Stroke Prevention in Nonvalvular Atrial Fibrillation: Answers to Challenging “Real-World” Questions  [PDF]
Jorge Ferreira,Daniel Ferreira,Miguel Viana-Baptista,Paulo Bettencourt,Rui Cernadas,Francisco Crespo
Thrombosis , 2012, DOI: 10.1155/2012/867121
Abstract: Dabigatran etexilate is a novel, oral, reversible, direct thrombin inhibitor that constitutes a major breakthrough for stroke prevention in patients with nonvalvular atrial fibrillation (AF). Dabigatran was the first new oral anticoagulant approved in Europe and became available in Portugal, for stroke prevention in nonvalvular AF, earlier than in most European countries. This paper is the joint effort of a panel of experts from different specialties and provides information on the use of dabigatran, in anticipation of the challenges that will come with increased usage. 1. Introduction Dabigatran etexilate (designated as dabigatran from here onwards) and other new oral anticoagulants (OACs) constitute a major breakthrough for stroke prevention in patients with nonvalvular atrial fibrillation (AF). They have been shown to be an alternative to vitamin K antagonists (VKAs) that does not require routine laboratory control. Dabigatran (Pradaxa?, Boehringer Ingelheim, Ingelheim, Germany) is a reversible direct thrombin inhibitor and, in the RE-LY trial (Randomized Evaluation of Long-term anticoagulation therapY), a phase III study, 150?mg bid was more effective in terms of stroke prevention in nonvalvular AF than VKA, whereas 110?mg bid was as effective as VKA, with a lower risk of bleeding [1]. Soon after the completion of this trial, the US Food and Drug Administration (FDA) approved dabigatran 150?mg bid and 75?mg bid (for patients with a creatinine clearance of 15 to 30?mL/min) [2]. Subsequently, the European Medicines Agency approved the doses of 150?mg bid and 110?mg bid (for patients aged at least 80 years, with an elevated risk of bleeding or receiving verapamil) [3] as an alternative to warfarin for stroke and systemic embolism (SE) reduction in patients with nonvalvular AF. The American College of Chest Physicians (ACCP) Guidelines on Antithrombotic Therapy and Prevention of Thrombosis (9th ed) suggest dabigatran 150?mg twice daily rather than adjusted-dose VKA for patients with nonvalvular AF [4]. Moreover, recent quantitative benefit-harm and economic analyses in the UK support regulatory decisions that dabigatran offers a positive benefit to harm ratio when compared to warfarin [5]. Despite considerable variation among different countries, stroke has been appointed as the second leading cause of death worldwide [6]. Portugal was ranked the highest among Western European countries in terms of stroke mortality [7], and available data suggests that stroke not only continues to be the leading cause of death in this country [8], but also that its
Left Atrial Appendage Closure for Stroke Prevention in Patients with Atrial Fibrillation and Hereditary Hemorrhagic Telangiectasia
Sebastiaan Velthuis,Martin J. Swaans,Johannes J. Mager,Benno J. W. M. Rensing,Lucas V. A. Boersma,Martijn C. Post
Case Reports in Cardiology , 2012, DOI: 10.1155/2012/646505
Abstract: Atrial fibrillation (AF) is the most common cardiac arrhythmia, affecting millions of individuals worldwide, and a major risk factor for disabling cerebral embolic stroke. Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant inherited disorder, characterized by vascular abnormalities with high-bleeding tendency and therefore intolerance for oral anticoagulation. We report a case of percutaneous closure of the left atrial appendage, which might be a good alternative strategy instead of chronic oral anticoagulation to protect patients with high-risk AF and HHT from cerebral embolic strokes.
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