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Risk Profiles and Antithrombotic Treatment of Patients Newly Diagnosed with Atrial Fibrillation at Risk of Stroke: Perspectives from the International, Observational, Prospective GARFIELD Registry  [PDF]
Ajay K. Kakkar, Iris Mueller, Jean-Pierre Bassand, David A. Fitzmaurice, Samuel Z. Goldhaber, Shinya Goto, Sylvia Haas, Werner Hacke, Gregory Y. H. Lip, Lorenzo G. Mantovani, Alexander G. G. Turpie, Martin van Eickels, Frank Misselwitz, Sophie Rushton-Smith, Gloria Kayani, Peter Wilkinson, Freek W. A. Verheugt, for the GARFIELD Registry Investigators
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0063479
Abstract: Background Limited data are available on the characteristics, clinical management, and outcomes of patients with atrial fibrillation at risk of stroke, from a worldwide perspective. The aim of this study was to describe the baseline characteristics and initial therapeutic management of patients with non-valvular atrial fibrillation across the spectrum of sites at which these patients are treated. Methods and Findings The Global Anticoagulant Registry in the FIELD (GARFIELD) is an observational study of patients newly diagnosed with non-valvular atrial fibrillation. Enrollment into Cohort 1 (of 5) took place between December 2009 and October 2011 at 540 sites in 19 countries in Europe, Asia-Pacific, Central/South America, and Canada. Investigator sites are representative of the distribution of atrial fibrillation care settings in each country. Cohort 1 comprised 10,614 adults (≥18 years) diagnosed with non-valvular atrial fibrillation within the previous 6 weeks, with ≥1 investigator-defined stroke risk factor (not limited to those in existing risk-stratification schemes), and regardless of therapy. Data collected at baseline included demographics, medical history, care setting, nature of atrial fibrillation, and treatments initiated at diagnosis. The mean (SD) age of the population was 70.2 (11.2) years; 43.2% were women. Mean±SD CHADS2 score was 1.9±1.2, and 57.2% had a score ≥2. Mean CHA2DS2-VASc score was 3.2±1.6, and 8,957 (84.4%) had a score ≥2. Overall, 38.0% of patients with a CHADS2 score ≥2 did not receive anticoagulant therapy, whereas 42.5% of those at low risk (score 0) received anticoagulant therapy. Conclusions These contemporary observational worldwide data on non-valvular atrial fibrillation, collected at the end of the vitamin K antagonist-only era, indicate that these drugs are frequently not being used according to stroke risk scores and guidelines, with overuse in patients at low risk and underuse in those at high risk of stroke. Trial Registration ClinicalTrials.gov TRI08888
Management of patients with atrial fibrillation at high risk of stroke: current treatment options  [cached]
Edwards D,Harris K,Mant J
Research Reports in Clinical Cardiology , 2012,
Abstract: Duncan Edwards, Keara Harris, Jonathan MantPrimary Care Unit, University of Cambridge, Cambridge, UKAbstract: Atrial fibrillation (AF) is common, and is associated with an increased risk of stroke. Patients' absolute risk of stroke depends on the presence or absence of additional risk factors as well as AF, including prior thromboembolism, increased age, hypertension, diabetes, structural heart disease, and female sex. The risk to benefit ratio of stroke prevention therapy differs according to the patients' absolute risk. There is evidence that even those with an estimated annual stroke risk of 2%–4%, who were once classified as medium risk, would benefit from anticoagulation and should be included in an expanded high-risk category. Alternatives to anticoagulation include the restoration of sinus rhythm and left atrial appendage surgery, but these may not be suitable for many high-risk patients with comorbidities. Antiplatelets are substantially less effective than anticoagulation and cause similar rates of bleeding. Self-monitoring and computerized decision support increases the time in therapeutic range and effectiveness of vitamin K antagonists. Novel oral anticoagulants including dabigatran, rivoraxaban, and apixaban have been shown to be noninferior to warfarin, do not require monitoring, and increase the prescribing options for stroke prevention in AF.Keywords: stroke prevention, atrial fibrillation, anticoagulants, primary prevention
Management of patients with atrial fibrillation at high risk of stroke: current treatment options
Edwards D, Harris K, Mant J
Research Reports in Clinical Cardiology , 2012, DOI: http://dx.doi.org/10.2147/RRCC.S16754
Abstract: nagement of patients with atrial fibrillation at high risk of stroke: current treatment options Review (2165) Total Article Views Authors: Edwards D, Harris K, Mant J Published Date June 2012 Volume 2012:3 Pages 35 - 47 DOI: http://dx.doi.org/10.2147/RRCC.S16754 Received: 16 February 2012 Accepted: 08 March 2012 Published: 25 June 2012 Duncan Edwards, Keara Harris, Jonathan Mant Primary Care Unit, University of Cambridge, Cambridge, UK Abstract: Atrial fibrillation (AF) is common, and is associated with an increased risk of stroke. Patients' absolute risk of stroke depends on the presence or absence of additional risk factors as well as AF, including prior thromboembolism, increased age, hypertension, diabetes, structural heart disease, and female sex. The risk to benefit ratio of stroke prevention therapy differs according to the patients' absolute risk. There is evidence that even those with an estimated annual stroke risk of 2%–4%, who were once classified as medium risk, would benefit from anticoagulation and should be included in an expanded high-risk category. Alternatives to anticoagulation include the restoration of sinus rhythm and left atrial appendage surgery, but these may not be suitable for many high-risk patients with comorbidities. Antiplatelets are substantially less effective than anticoagulation and cause similar rates of bleeding. Self-monitoring and computerized decision support increases the time in therapeutic range and effectiveness of vitamin K antagonists. Novel oral anticoagulants including dabigatran, rivoraxaban, and apixaban have been shown to be noninferior to warfarin, do not require monitoring, and increase the prescribing options for stroke prevention in AF.
Genetics of Atrial Fibrillation and Possible Implications for Ischemic Stroke  [PDF]
Robin Lemmens,Sylvia Hermans,Dieter Nuyens,Vincent Thijs
Stroke Research and Treatment , 2011, DOI: 10.4061/2011/208694
Abstract: Atrial fibrillation is the most common cardiac arrhythmia mainly caused by valvular, ischemic, hypertensive, and myopathic heart disease. Atrial fibrillation can occur in families suggesting a genetic background especially in younger subjects. Additionally recent studies have identified common genetic variants to be associated with atrial fibrillation in the general population. This cardiac arrhythmia has important public health implications because of its main complications: congestive heart failure and ischemic stroke. Since atrial fibrillation can result in ischemic stroke, one might assume that genetic determinants of this cardiac arrhythmia are also implicated in cerebrovascular disease. Ischemic stroke is a multifactorial, complex disease where multiple environmental and genetic factors interact. Whether genetic variants associated with a risk factor for ischemic stroke also increase the risk of a particular vascular endpoint still needs to be confirmed in many cases. Here we review the current knowledge on the genetic background of atrial fibrillation and the consequences for cerebrovascular disease. 1. Introduction Of all cardiac arrhythmias, atrial fibrillation (AF) is the most common, affecting approximately 1-2% of the population [1]. The prevalence is higher in men compared to women and increases with age, which is reflected by the finding that 25% of the population aged over 40 will develop AF [2]. Patients with AF frequently have other cardiovascular and noncardiovascular comorbidities, the most important condition being hypertension [3], which is an important risk factor for the development of AF [4]. AF is not a benign disease as it is associated with increased rates of death, stroke, ischemic heart disease, heart failure, and peripheral thrombo-embolic events. In patients with AF, various independent factors raise the risk of stroke such as the presence of hypertension, advancing age and diabetes and the previous occurrence of a stroke or transient ischemic attack (TIA) [5, 6]. Epidemiological studies have identified various risk factors for AF which include age, male sex, hypertension and the presence of structural heart abnormalities. However, it was suspected that the totality of the risk could not be explained exclusively by these factors, and a genetic risk component was suspected [7]. Although the vast majority of AF is sporadic and nonfamilial, familial (hereditary) forms of AF have been identified (Table 1). Also, the genetic background of AF in the general population has been studied through association studies (Table 1). Since
Atrial fibrillation in patients with ischemic stroke: A population-based study  [cached]
Sandra Kruchov Thygesen,Lars Frost,Kim A Eagle,Søren Paaske Johnsen
Clinical Epidemiology , 2009,
Abstract: Sandra Kruchov Thygesen1, Lars Frost2, Kim A Eagle3, S ren Paaske Johnsen11Department of Clinical Epidemiology, Aarhus University Hospital, Denmark; 2Silkeborg Hospital and Clinical Institute, Aarhus University Hospital, Denmark; 3The Michigan Cardiovascular Research and Reporting Program, University of Michigan, Ann Arbor, MI, USABackground: Atrial fibrillation is a major risk factor for ischemic stroke. However, the prognostic impact of atrial fibrillation among patients with stroke is not fully clarified. We compared patient characteristics, including severity of stroke and comorbidity, quality of in-hospital care and outcomes in a cohort of first-time ischemic stroke patients with and without atrial fibrillation.Methods: Based on linkage of public medical databases, we did a population-based follow-up study among 3,849 stroke patients from the County of Aarhus, Denmark admitted in the period of 2003–2007 and prospectively registered in the Danish National Indicator Project.Results: Atrial fibrillation was associated with an adverse prognostic profile but not with an overall poorer quality of in-hospital care. Patients with atrial fibrillation had a longer total length of stay (median: 15 vs 9 days), and were at increased risk of in-hospital medical complications (adjusted relative risk = 1.48, 95% CI: 1.23–1.79) and recurrent stroke (adjusted hazard ratio = 1.30, 95% CI: 0.93–1.82) when compared with patients without atrial fibrillation. The adjusted hazard ratios for 30 days and one year mortality were 1.55 (95% CI: 1.20–2.01) and 1.55 (95% CI: 1.30–1.85), respectively. Patients not eligible to oral anticoagulant treatment had an increased risk of recurrent stroke (adjusted hazard ratio = 1.92, 95% CI: 1.19–3.11).Conclusion: Atrial fibrillation is associated with a poor outcome among patients with ischemic stroke particularly among patients, who are not eligible to oral anticoagulant treatment. Keywords: atrial fibrillation, stroke, quality of care, prognosis, mortality, epidemiology
Oral anticoagulation to reduce risk of stroke in patients with atrial fibrillation: current and future therapies  [cached]
Amin A
Clinical Interventions in Aging , 2013,
Abstract: Alpesh AminHospitalist Program, University of California, Irvine, Orange, CA, USAAbstract: Atrial fibrillation (AF) is associated with an increased incidence and severity of strokes. The burden of AF-related stroke is expected to increase in parallel with the aging of the population. Oral anticoagulation with warfarin has been the pharmacologic standard for stroke risk reduction in patients with AF. When used with close attention to dosing and monitoring, warfarin is effective prophylactic therapy against thromboembolic stroke. However, it is underused by physicians, in part because of the known risks of adverse events with warfarin. Consequently, many patients with AF live with an avoidably elevated risk of stroke. New options, ie, oral anticoagulants with novel mechanisms of action, have recently been approved to reduce the risk of stroke in AF, and others are in development. These newer agents may address some of the complexities of warfarin use while providing similar or better efficacy and safety.Keywords: atrial fibrillation, stroke, oral anticoagulants
Atrial fibrillation in patients with ischemic stroke: A population-based study
Sandra Kruchov Thygesen, Lars Frost, Kim A Eagle, S ren Paaske Johnsen
Clinical Epidemiology , 2009, DOI: http://dx.doi.org/10.2147/CLEP.S4794
Abstract: trial fibrillation in patients with ischemic stroke: A population-based study Original Research (5074) Total Article Views Authors: Sandra Kruchov Thygesen, Lars Frost, Kim A Eagle, S ren Paaske Johnsen Published Date May 2009 Volume 2009:1 Pages 55 - 65 DOI: http://dx.doi.org/10.2147/CLEP.S4794 Sandra Kruchov Thygesen1, Lars Frost2, Kim A Eagle3, S ren Paaske Johnsen1 1Department of Clinical Epidemiology, Aarhus University Hospital, Denmark; 2Silkeborg Hospital and Clinical Institute, Aarhus University Hospital, Denmark; 3The Michigan Cardiovascular Research and Reporting Program, University of Michigan, Ann Arbor, MI, USA Background: Atrial fibrillation is a major risk factor for ischemic stroke. However, the prognostic impact of atrial fibrillation among patients with stroke is not fully clarified. We compared patient characteristics, including severity of stroke and comorbidity, quality of in-hospital care and outcomes in a cohort of first-time ischemic stroke patients with and without atrial fibrillation. Methods: Based on linkage of public medical databases, we did a population-based follow-up study among 3,849 stroke patients from the County of Aarhus, Denmark admitted in the period of 2003–2007 and prospectively registered in the Danish National Indicator Project. Results: Atrial fibrillation was associated with an adverse prognostic profile but not with an overall poorer quality of in-hospital care. Patients with atrial fibrillation had a longer total length of stay (median: 15 vs 9 days), and were at increased risk of in-hospital medical complications (adjusted relative risk = 1.48, 95% CI: 1.23–1.79) and recurrent stroke (adjusted hazard ratio = 1.30, 95% CI: 0.93–1.82) when compared with patients without atrial fibrillation. The adjusted hazard ratios for 30 days and one year mortality were 1.55 (95% CI: 1.20–2.01) and 1.55 (95% CI: 1.30–1.85), respectively. Patients not eligible to oral anticoagulant treatment had an increased risk of recurrent stroke (adjusted hazard ratio = 1.92, 95% CI: 1.19–3.11). Conclusion: Atrial fibrillation is associated with a poor outcome among patients with ischemic stroke particularly among patients, who are not eligible to oral anticoagulant treatment.
Aortic Stiffness in Lone Atrial Fibrillation: A Novel Risk Factor for Arrhythmia Recurrence  [PDF]
Dennis H. Lau, Melissa E. Middeldorp, Anthony G. Brooks, Anand N. Ganesan, Kurt C. Roberts-Thomson, Martin K. Stiles, Darryl P. Leong, Hany S. Abed, Han S. Lim, Christopher X. Wong, Scott R. Willoughby, Glenn D. Young, Jonathan M. Kalman, Walter P. Abhayaratna, Prashanthan Sanders
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0076776
Abstract: Background Recent community-based research has linked aortic stiffness to the development of atrial fibrillation. We posit that aortic stiffness contributes to adverse atrial remodeling leading to the persistence of atrial fibrillation following catheter ablation in lone atrial fibrillation patients, despite the absence of apparent structural heart disease. Here, we aim to evaluate aortic stiffness in lone atrial fibrillation patients and determine its association with arrhythmia recurrence following radio-frequency catheter ablation. Methods We studied 68 consecutive lone atrial fibrillation patients who underwent catheter ablation procedure for atrial fibrillation and 50 healthy age- and sex-matched community controls. We performed radial artery applanation tonometry to obtain central measures of aortic stiffness: pulse pressure, augmentation pressure and augmentation index. Following ablation, arrhythmia recurrence was monitored at months 3, 6, 9, 12 and 6 monthly thereafter. Results Compared to healthy controls, lone atrial fibrillation patients had significantly elevated peripheral pulse pressure, central pulse pressure, augmentation pressure and larger left atrial dimensions (all P<0.05). During a mean follow-up of 2.9±1.4 years, 38 of the 68 lone atrial fibrillation patients had atrial fibrillation recurrence after initial catheter ablation procedure. Neither blood pressure nor aortic stiffness indices differed between patients with and without atrial fibrillation recurrence. However, patients with highest levels (≥75th percentile) of peripheral pulse pressure, central pulse pressure and augmentation pressure had higher atrial fibrillation recurrence rates (all P<0.05). Only central aortic stiffness indices were associated with lower survival free from atrial fibrillation using Kaplan-Meier analysis. Conclusion Aortic stiffness is an important risk factor in patients with lone atrial fibrillation and contributes to higher atrial fibrillation recurrence following catheter ablation procedure.
Left Atrial Appendage Exclusion for Stroke Prevention in Atrial Fibrillation  [PDF]
Taral K. Patel,Clyde W. Yancy,Bradley P. Knight
Cardiology Research and Practice , 2012, DOI: 10.1155/2012/610827
Abstract: The public health burden of atrial fibrillation (AF) and associated thromboembolic stroke continues to grow at alarming rates. AF leads to a fivefold increase in the risk of stroke. Therefore, stroke prevention remains the most critical aspect of AF management. Current standard of care focuses on oral systemic anticoagulation, most commonly with warfarin and now with newer agents such as dabigatran, rivaroxaban, and apixaban. However, the challenges and limitations of oral anticoagulation have been well documented. Given the critical role of the left atrial appendage (LAA) in the genesis of AF-related thromboembolism, recent efforts have targeted removal or occlusion of the LAA as an alternative strategy for stroke prevention, particularly in patients deemed unsuitable for oral anticoagulation. This paper highlights recent advances in mechanical exclusion of the LAA. The problem of AF and stroke is briefly summarized, followed by an explanation for the rationale behind LAA exclusion for stroke prevention. After briefly reviewing the history of LAA exclusion, we highlight the most promising LAA exclusion devices currently available. Finally, we discuss future challenges and opportunities in this growing field. 1. Introduction: Atrial Fibrillation and Stroke Atrial fibrillation (AF) is the most common arrhythmia in modern clinical practice, currently affecting up to 5 million people in the United States [1, 2]. The prevalence rises sharply with age, from approximately 1% among people aged 55–59 years to over 10% among those aged greater than 80 years [3]. Importantly, the burden of AF is expected to rise threefold by 2050 to an estimated 12–16 million Americans [4]. The most feared clinical consequence of AF is stroke due to thromboembolism. Stroke is the third leading cause of death and the number one cause of major disability in the United States [5]. AF is a powerful risk factor for stroke; a diagnosis of AF increases stroke risk fivefold and conveys an overall stroke rate of 5% per year [5]. Of the estimated 800,000 annual strokes in the USA, the percentage attributable to AF ranges from 1.5% (50–59 years old) to 23.5% (80–89 years old) [5]. As AF is commonly silent and undiagnosed, the influence of AF on stroke is almost certainly underestimated. 2. The Role of the Left Atrial Appendage AF promotes thromboembolism through a variety of mechanisms, most significantly mechanical dysfunction in the atria leading to impaired blood flow and stasis. Additional factors including endothelial dysfunction, inflammation, platelet activation, and a
Frequent Periodic Leg Movement During Sleep Is an Unrecognized Risk Factor for Progression of Atrial Fibrillation  [PDF]
Mahek Mirza, Win-Kuang Shen, Aamir Sofi, Canh Tran, Ahad Jahangir, Sulaiman Sultan, Uzma Khan, Maria Viqar, Chi Cho, Arshad Jahangir
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0078359
Abstract: Sleep apnea has been recognized as a factor predisposing to atrial fibrillation recurrence and progression. The effect of other sleep-disturbing conditions on atrial fibrillation progression is not known. We sought to determine whether frequent periodic leg movement during sleep is a risk factor for progression of atrial fibrillation. In this retrospective study, patients with atrial fibrillation and a clinical suspicion of restless legs syndrome who were referred for polysomnography were divided into two groups based on severity of periodic leg movement during sleep: frequent (periodic movement index >35/h) and infrequent (≤35/h). Progression of atrial fibrillation to persistent or permanent forms between the two groups was compared using Wilcoxon rank-sum test, chi-square tests and logistic regression analysis. Of 373 patients with atrial fibrillation (77% paroxysmal, 23% persistent), 108 (29%) progressed to persistent or permanent atrial fibrillation during follow-up (median, 33 months; interquartile range, 16-50). Compared to patients with infrequent periodic leg movement during sleep (n=168), patients with frequent periodic leg movement during sleep (n=205) had a higher rate of atrial fibrillation progression (23% vs. 34%; p=0.01). Patients with frequent periodic leg movement during sleep were older and predominantly male; however, there were no significant differences at baseline in clinical factors that promote atrial fibrillation progression between both groups. On multivariate analysis, independent predictors of atrial fibrillation progression were persistent atrial fibrillation at baseline, female gender, hypertension and frequent periodic leg movement during sleep. In patients with frequent periodic leg movement during sleep, dopaminergic therapy for control of leg movements in patients with restless legs syndrome reduced risk of atrial fibrillation progression. Frequent leg movement during sleep in patients with restless legs syndrome is associated with progression of atrial fibrillation to persistent and permanent forms.
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