title: Cost-Effectiveness of Dabigatran for Stroke Prophylaxis in Atrial Fibrillation Dabigatran etexilate versus warfarin in management of non-valvular atrial fibrillation in UK context: quantitative benefit-harm and economic analyses Stroke with intermittent atrial fibrillation: incidence and predictors during aspirin therapy. Stroke Prevention in Atrial Fibrillation Investigators. Cost-effectiveness of dabigatran etexilate for the prevention of stroke and systemic embolism in atrial fibrillation: a Canadian payer perspective. Cost Effectiveness of Warfarin Versus Aspirin in Patients Older Than 75 Years With Atrial Fibrillation Factors associated with ischemic stroke during aspirin therapy in atrial fibrillation: analysis of 2012 participants in the SPAF I-III clinical trials. The Stroke Prevention in Atrial Fibrillation (SPAF) Investigators. Effect of Age on Stroke Prevention Therapy in Patients With Atrial Fibrillation: The Atrial Fibrillation Investigators 2012 focused update of the ESC Guidelines for the management of atrial fibrillation: an update of the 2010 ESC Guidelines for the management of atrial fibrillation. Developed with the special contribution of the European Heart Rhythm Association. Gender Differences in the Risk of Ischemic Stroke and Peripheral Embolism in Atrial Fibrillation: The AnTicoagulation and Risk factors In Atrial fibrillation (ATRIA) Study Performance of stroke risk scores in older people with atrial fibrillation not taking warfarin: comparative cohort study from BAFTA trial Feasibility of TEE-guided stroke risk assessment in atrial fibrillation—background, aims, design and baseline data of the TIARA pilot study Risk factors for new thromboembolic stroke in patients > or = 62 years of age with chronic atrial fibrillation. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. A longitudinal population-based study of prothrombotic factors in elderly subjects with atrial fibrillation: the Rotterdam Study 1990-1999. Risk factors for thromboembolic stroke in elderly patients with chronic atrial fibrillation. Predictors of major vascular events in patients with a transient ischemic attack or minor ischemic stroke and with nonrheumatic atrial fibrillation. European Atrial Fibrillation Trial (EAFT) Study Group. Transesophageal Echocardiography To Assess Embolic Risk in Patients with Atrial Fibrillation Risk factors for stroke in patients with nonrheumatic atrial fibrillation: a case-control study. Impact of vascular disease in predicting stroke and death in patients with atrial fibrillation: the Danish Diet, Cancer and Health cohort study. Warfarin versus aspirin for stroke prevention in an elderly community population with atrial fibrillation (the Birmingham Atrial Fibrillation Treatment of the Aged Study, BAFTA): a randomised controlled trial Cost-effectiveness of warfarin and aspirin for prophylaxis of stroke in patients with nonvalvular atrial fibrillation. Echocardiographic predictors of stroke in patients with atrial fibrillation: a prospective study of 1066 patients from 3 clinical trials. Anticoagulation therapy for stroke prevention in atrial fibrillation: how well do randomized trials translate into clinical practice? Prevalence, incidence and lifetime risk of atrial fibrillation: the Rotterdam study. Cost-Effectiveness of Dabigatran Compared With Warfarin for Stroke Prevention in Atrial Fibrillation Cost-effectiveness of warfarin: trial versus "real-world" stroke prevention in atrial fibrillation. Risk factors for thromboembolic complications in chronic atrial fibrillation. The Copenhagen AFASAK study. Assessment of three schemes for stratifying stroke risk in patients with nonvalvular atrial fibrillation. Comparative validation of a novel risk score for predicting bleeding risk in anticoagulated patients with atrial fibrillation: the HAS-BLED (Hypertension, Abnormal Renal/Liver Function, Stroke, Bleeding History or Predisposition, Labile INR, Elderly, Drugs/Alcohol Concomitantly) score.
abstract: Background — Recent studies have investigated alternatives to warfarin for stroke prophylaxis in patients with atrial fibrillation ( AF ) , but whether these alternatives are cost-effective is unknown . Methods and Results — On the basis of the results from R and omized Evaluation of Long Term Anticoagulation Therapy ( RE-LY ) and other trials , we developed a decision- analysis model to compare the cost and quality -adjusted survival of various antithrombotic therapies . We ran our Markov model in a hypothetical cohort of 70-year-old patients with AF using a cost-effectiveness threshold of $ 50 000/ quality -adjusted life-year . We estimated the cost of dabigatran as US $ 9 a day . For a patient with an average risk of major hemorrhage ( ≈3%/y ) , the most cost-effective therapy depended on stroke risk . For patients with the lowest stroke rate ( CHADS2 stroke score of 0 ) , only aspirin was cost-effective . For patients with a moderate stroke rate ( CHADS2 score of 1 or 2 ) , warfarin was cost-effective unless the risk of hemorrhage was high or quality of international normalized ratio control was poor ( time in the therapeutic range < 57.1 % ) . For patients with a high stroke risk ( CHADS2 stroke score ≥3 ) , dabigatran 150 mg ( twice daily ) was cost-effective unless international normalized ratio control was excellent ( time in the therapeutic range > 72.6 % ) . Neither dabigatran 110 mg nor dual therapy ( aspirin and clopidogrel ) was cost-effective . Conclusions — Dabigatran 150 mg ( twice daily ) was cost-effective in AF population s at high risk of hemorrhage or high risk of stroke unless international normalized ratio control with warfarin was excellent . Warfarin was cost-effective in moderate-risk AF population s unless international normalized ratio control was poor Objectives To determine the incremental net health benefits of dabigatran etexilate 110 mg and 150 mg twice daily and warfarin in patients with non-valvular atrial fibrillation and to estimate the cost effectiveness of dabigatran in the United Kingdom . Design Quantitative benefit-harm and economic analyses using a discrete event simulation model to extrapolate the findings of the RE-LY ( R and omized Evaluation of Long-Term Anticoagulation Therapy ) study to a lifetime horizon . Setting UK National Health Service . Population Cohorts of 50 000 simulated patients at moderate to high risk of stroke with a mean baseline CHADS2 ( Congestive heart failure , Hypertension , Age≥75 years , Diabetes mellitus , previous Stroke/transient ischaemic attack ) score of 2.1 . Main outcome measures Quality adjusted life years ( QALYs ) gained and incremental cost per QALY of dabigatran compared with warfarin . Results Compared with warfarin , low dose and high dose dabigatran were associated with positive incremental net benefits of 0.094 ( 95 % central range −0.083 to 0.267 ) and 0.146 ( −0.029 to 0.322 ) QALYs . Positive incremental net benefits result ed for high dose dabigatran in 94 % of simulations versus warfarin and in 76 % of those versus low dose dabigatran . In the economic analysis , high dose dabigatran dominated the low dose , had an incremental cost effectiveness ratio of £ 23 082 ( € 26 700 ; $ 35 800 ) per QALY gained versus warfarin , and was more cost effective in patients with a baseline CHADS2 score of 3 or above . However , at centres that achieved good control of international normalised ratio , such as those in the UK , dabigatran 150 mg was not cost effective , at £ 42 386 per QALY gained . Conclusions This analysis supports regulatory decisions that dabigatran offers a positive benefit to harm ratio when compared with warfarin . However , no subgroup for which dabigatran 110 mg offered any clinical or economic advantage over 150 mg was identified . High dose dabigatran will be cost effective only for patients at increased risk of stroke or for whom international normalised ratio is likely to be less well controlled OBJECTIVE This study was performed to characterize the risk of stroke in elderly patients with recurrent intermittent atrial fibrillation ( AF ) . BACKGROUND Although intermittent AF is common , relatively little is known about the attendant risk of stroke . METHODS A longitudinal cohort study was performed comparing 460 participants with intermittent AF with 1,552 with sustained AF treated with aspirin in the Stroke Prevention in Atrial Fibrillation studies and followed for a mean of two years . Independent risk factors for ischemic stroke were identified by multivariate analysis . RESULTS Patients with intermittent AF were , on average , younger ( 66 vs. 70 years , p < 0.001 ) , were more often women ( 37 % vs. 26 % p < 0.001 ) and less often had heart failure ( 11 % vs. 21 % , p < 0.001 ) than those with sustained AF . The annualized rate of ischemic stroke was similar for those with intermittent ( 3.2 % ) and sustained AF ( 3.3 % ) . In patients with intermittent AF , independent predictors of ischemic stroke were advancing age ( relative risk [ RR ] = 2.1 per decade , p < 0.001 ) , hypertension ( RR = 3.4 , p = 0.003 ) and prior stroke ( RR = 4.1 , p = 0.01 ) . Of those with intermittent AF predicted to be high risk ( 24 % ) , the observed stroke rate was 7.8 % per year ( 95 % confidence interval 4.5 to 14 ) . CONCLUSIONS In this large cohort of AF patients given aspirin , those with intermittent AF had stroke rates similar to patients with sustained AF and similar stroke risk factors . Many elderly patients with recurrent intermittent AF have substantial rates of stroke and likely benefit from anticoagulation . High-risk patients with intermittent AF can be identified using the same clinical criteria that apply to patients with sustained AF Oral dabigatran etexilate is indicated for the prevention of stroke and systemic embolism in patients with atrial fibrillation ( AF ) in whom anticoagulation is appropriate . Based on the RE-LY study we investigated the cost-effectiveness of Health Canada approved dabigatran etexilate dosing ( 150 mg bid for patients < 80 years , 110 mg bid for patients ≥80 years ) versus warfarin and " real-world " prescribing ( i.e. warfarin , aspirin , or no treatment in a cohort of warfarin-eligible patients ) from a Canadian payer perspective . A Markov model simulated AF patients at moderate to high risk of stroke while tracking clinical events [ primary and recurrent ischaemic strokes , systemic embolism , transient ischaemic attack , haemorrhage ( intracranial , extracranial , and minor ) , acute myocardial infa rct ion and death ] and result ing functional disability . Acute event costs and result ing long-term follow-up costs incurred by disabled stroke survivors were based on a Canadian prospect i ve study , published literature , and national statistics . Clinical events , summarized as events per 100 patient-years , quality -adjusted life years ( QALYs ) , total costs , and incremental cost effectiveness ratios ( ICER ) were calculated . Over a lifetime , dabigatran etexilate treated patients experienced fewer intracranial haemorrhages ( 0.49 dabigatran etexilate vs. 1.13 warfarin vs. 1.05 " real-world " prescribing ) and fewer ischaemic strokes ( 4.40 dabigatran etexilate vs. 4.66 warfarin vs. 5.16 " real-world " prescribing ) per 100 patient-years . The ICER  of dabigatran etexilate was $ 10,440/QALY versus warfarin and $ 3,962/QALY versus " real-world " prescribing . This study demonstrates that dabigatran etexilate is a highly cost-effective alternative to current care for the prevention of stroke and systemic embolism among Canadian AF patients Background and Purpose — Oral anticoagulants are effective at reducing stroke compared with aspirin in atrial fibrillation patients older than 75 years . Although the benefits of reduced stroke risk outweigh the risks of bleeding , the cost effectiveness of warfarin in this patient population has not yet been established . Methods — An economic evaluation was conducted alongside a r and omized , controlled trial ; 973 patients ≥75 years of age with atrial fibrillation were recruited from primary care and r and omly assigned to either take warfarin or aspirin . Follow-up was for a mean of 2.7 years . Costs of thrombotic and hemorrhagic events , anticoagulation clinic visits , and primary care utilization were determined . Clinical benefits were expressed in terms of a primary event avoided : fatal/nonfatal disabling stroke , intracranial hemorrhage , or systemic embolism . A cost-utility analysis was performed using quality -adjusted life years as the benefit measure . Results — Total costs over 4 years were lower in the warfarin group ( difference , −£165 ; 95 % CI , −£452–£89 ) , primarily driven by the difference in primary event costs . The primary event rate over 4 years was lower in the warfarin group ( 0.049 versus 0.099 ) , and the quality -adjusted life years score was higher ( difference , 0.02 ; 95 % CI , −0.07–0.11 ) . With lower costs and a higher quality -adjusted life years score , warfarin is the dominant treatment , but the differences in both costs and effects are small . Conclusions — Warfarin is cost-effective compared with aspirin in atrial fibrillation patients age ≥75 years . These data support the anticoagulant therapy option in this high-risk patient population . However , the small differences in costs and effects indicate the importance of exploring patient preferences BACKGROUND AND PURPOSE Nonvalvular atrial fibrillation ( AF ) is a strong , independent risk factor for stroke , but the absolute rate of stroke varies widely among AF patients , importantly influencing the potential benefit of antithrombotic prophylaxis . We explore factors associated with ischemic stroke in AF patients taking aspirin .  METHODS We performed multivariate logistic regression analysis of 2012 participants given aspirin alone or in combination with low , inefficacious doses of warfarin in the Stroke Prevention in Atrial Fibrillation I-III trials followed for a mean of 2.0 years , during which 130 ischemic strokes were observed . RESULTS Age ( relative risk [RR]=1.8 per decade , P<0.001 ) , female sex ( RR=1.6 , P=0.01 ) , history of hypertension ( RR=2.0 , P<0.001 ) , systolic blood pressure > 160 mm Hg ( RR=2.3 , P<0.001 ) , and prior stroke or transient ischemic attack ( RR=2.9 , P<0.001 ) were independently associated with increased stroke risk . Regular consumption of > /=14 alcohol-containing drinks per week was associated with reduced stroke risk ( adjusted RR=0.4 , P=0.04 ) . Among SPAF III participants , estrogen hormone replacement therapy was associated with a higher risk of ischemic stroke ( adjusted RR=3.2 , P=0.007 ) . With the use of these variables , a risk stratification scheme for primary prevention separated participants into those with high ( 7.1%/y , 22 % of the cohort ) , moderate ( 2.6%/y , 37 % of the cohort ) , and low ( 0.9%/y , 41 % of the cohort ) rates of stroke . Ischemic strokes in low-risk participants were less often disabling ( P<0.001 ) . CONCLUSIONS Patients with AF who have high and low rates of stroke during treatment with  aspirin can be identified . However , validation of our risk stratification scheme is necessary before it can be applied with confidence to clinical management . Postmenopausal estrogen replacement therapy and moderate alcohol consumption may additionally modify the risk of stroke in AF , but these findings require confirmation Background and Purpose — Stroke risk increases with age in patients who have nonvalvular atrial fibrillation . It is uncertain whether the efficacy of stroke prevention therapies in atrial fibrillation changes as patients age . The objective of this study was to determine the effect of age on the relative efficacy of oral anticoagulants ( OAC ) and antiplatelet ( AP ) therapy ( including acetylsalicylic acid and triflusal ) on ischemic stroke , serious bleeding , and vascular events in patients with atrial fibrillation . Methods — This is an analysis of the Atrial Fibrillation Investigators data base , which contains patient level- data from r and omized trials of stroke prevention in atrial fibrillation . We used Cox regression models with age as a continuous variable that controlled for sex , year of r and omization , and history of cerebrovascular disease , diabetes , hypertension , and congestive heart failure . Outcomes included ischemic stroke , serious bleeding ( intracranial hemorrhage or systemic bleeding requiring hospitalization , transfusion , or surgery ) , and cardiovascular events ( ischemic stroke , myocardial infa rct ion , systemic embolism , or vascular death ) . Results — The analysis included 8932 patients and 17 685 years of observation from 12 trials . Patient age increased risk of ischemic stroke ( adjusted hazard ratio per decade increase 1.45 ; 95 % CI , 1.26 to 1.66 ) , serious bleeding ( 1.61 ; 1.47 to 1.77 ) , and cardiovascular events ( 1.43 ; 1.33 to 1.53 ) . Compared with placebo , OAC and AP significantly reduced the risk of ischemic stroke ( OAC , 0.36 ; 0.29 to 0.45 ; AP , 0.81 ; 0.72 to 0.90 ) and cardiovascular outcomes ( OAC , 0.59 ; 0.52 to 0.66 ; AP , 0.81 ; 0.75 to 0.88 ) , whereas OAC increased risk of serious bleeding ( 1.56 ; 1.03 to 2.37 ) . The relative benefit of OAC versus placebo or AP did not vary by patient age for any outcome . Compared with placebo , the relative benefit of AP  for preventing ischemic stroke decreased significantly as patients aged ( P=0.01 ) . Conclusions — As patients with atrial fibrillation age , the relative efficacy of AP to prevent ischemic stroke appears to decrease , whereas it does not change for OAC . Because stroke risk increases with age , the absolute benefit of OAC increases as patients get older ACCF : American College of Cardiology Foundation ACCP : American College of Chest Physicians ACS : acute coronary syndrome ACT : Atrial arrhythmia Conversion Trial ADONIS : American – Australian – African trial with DronedarONe In atrial fibrillation or flutter for the maintenance of Sinus rhythm AF : atrial fibrillation AHA : American Heart Association AND ROMEDA : ANtiarrhythmic trial with DROnedarone in Moderate-to-severe congestive heart failure Evaluating morbidity DecreAse APHRS : Asia Pacific Heart Rhythm Society aPTT : activated partial thromboplastin time ARB : angiotensin-receptor blocker ARISTOTLE : Apixaban for Reduction In STroke and Other ThromboemboLic Events in atrial fibrillation ATHENA : A placebo-controlled , double-blind , parallel arm Trial to assess the efficacy of dronedarone 400 mg b.i.d . for the prevention of cardiovascular Hospitalization or death from any cause in patiENts with Atrial fibrillation/atrial flutter ATRIA : AnTicoagulation and Risk factors In Atrial fibrillation AVERROES : Apixaban VErsus acetylsalicylic acid ( ASA ) to Reduce the Rate Of Embolic Stroke in atrial fibrillation patients who have failed or are unsuitable for vitamin K antagonist treatment AVRO : A prospect i ve , r and omized , double-blind , Active-controlled , superiority study of Vernakalant vs. amiodarone in Recent Onset atrial fibrillation b.i.d : bis in die ( twice daily ) b.p.m . : beats per minute CABANA : Catheter ABlation vs . ANtiarrhythmic drug therapy for Atrial fibrillation CABG : coronary artery bypass graft CAP : Continued Access to Protect AF CHA2DS2-VASc : Congestive heart failure or left ventricular dysfunction Hypertension , Age ≥75 ( doubled ) , Diabetes , Stroke (doubled)-Vascular disease , Age 65–74 , Sex category ( female ) CHADS2 : Congestive heart failure , Hypertension , Age ≥75 , Diabetes , Stroke ( doubled ) CI : confidence interval CRAFT : Controlled R and omized Atrial Fibrillation Trial CrCl : creatinine clearance DAFNE : Dronedarone Atrial FibrillatioN study after Electrical cardioversion DIONYSOS : R and omized Double blind trIal to evaluate efficacy and safety of drOnedarone ( 400 mg b.i.d . ) vs . amiodaroNe ( 600 mg q.d . for 28 daYS , then 200 mg qd thereafter ) for at least 6 mOnths for the maintenance of Sinus rhythm in patients with atrial fibrillation EAST : Early treatment of Atrial fibrillation for Stroke prevention Trial EHRA : European Heart Rhythm Association ECG : electrocardiogram EMA : European Medicines Agency ERATO : Efficacy and safety of dRonedArone for The cOntrol of ventricular rate during atrial fibrillation EURIDIS : EURopean trial In atrial fibrillation or flutter patients receiving Dronedarone for the maIntenance of Sinus rhythm FAST : atrial Fibrillation catheter Ablation vs . Surgical ablation Treatment FDA : Food and Drug Administration Flec-SL : Flecainide Short-Long trial HAS-BLED : Hypertension , Abnormal renal/liver function , Stroke , Bleeding history or predisposition , Labile INR , Elderly , Drugs/alcohol concomitantly HF-PEF : heart failure with preserved ejection fraction HF-REF : heart failure with reduced ejection fraction HR : hazard ratio HRS : Heart Rhythm Society ICH : intracranial haemorrhage INR : international normalized ratio i.v . : intravenous J-RHYTHM : Japanese RHYTHM management trial for atrial fibrillation LAA : left atrial appendage LoE : level of evidence LVEF : left ventricular ejection fraction MANTRA-PAF : Medical ANtiarrhythmic Treatment or Radiofrequency Ablation in Paroxysmal Atrial Fibrillation NICE : National Institute for Health and Clinical Excellence NOAC : novel oral anticoagulant NSAID : non-steroidal anti-inflammatory drug NYHA : New York Heart Association OAC : oral anticoagulant or oral anticoagulation o.d . : omni die ( every day ) PALLAS : Permanent Atrial fibriLLAtion outcome Study using dronedarone on top of st and ard therapy PCI : percutaneous coronary intervention PREVAIL : Prospect i ve R and omized EVAluation of the LAA closure device In patients with atrial fibrillation v s. Long-term warfarin therapy PROTECT AF : WATCHMAN LAA system for embolic PROTECTion in patients with Atrial Fibrillation PT : prothrombin time RAAFT : Radio frequency Ablation Atrial Fibrillation Trial RE-LY : R and omized Evaluation of Long-term anticoagulant therapY with dabigatran etexilate ROCKET-AF : Rivaroxaban Once daily oral direct factor Xa inhibition Compared with vitamin K antagonism for prevention of stroke and Embolism Trial in atrial fibrillation RRR : relative risk reduction TE : thromboembolism TIA : transient ischaemic attack t.i.d . : ter in die ( three times daily ) TOE : transoesophageal echocardiogram TTR : time in therapeutic range VKA : vitamin K antagonist Guidelines summarize and evaluate all currently available evidence on a particular issue with the aim of assisting physicians in selecting the best management strategy for an individual patient suffering from a given condition , taking into account the impact on Background —Previous studies provide conflicting results about whether women are at higher risk than men for thromboembolism in the setting of atrial fibrillation ( AF ) . We examined data from a large contemporary cohort of AF patients to address this question . Methods and Results —We prospect ively studied 13 559 adults with AF and recorded data on patients ’ clinical characteristics and the occurrence of incident hospitalizations for ischemic stroke , peripheral embolism , and major hemorrhagic events through search ing vali date d computerized data bases and medical record review . We compared event rates by patient sex using multivariable log-linear regression , adjusting for clinical risk factors for stroke , and stratifying by warfarin use . We identified 394  ischemic stroke and peripheral embolic events during 15 494 person-years of follow-up off warfarin . After multivariable analysis , women had higher annual rates of thromboembolism off warfarin than did men ( 3.5 % versus 1.8 % ; adjusted rate ratio [ RR ] , 1.6 ; 95 % CI , 1.3 to 1.9 ) . There was no significant difference by sex in 30-day mortality after thromboembolism ( 23 % for both ) . Warfarin use was associated with significantly lower adjusted thromboembolism rates for both women and men ( RR , 0.4 ; 95 % CI , 0.3 to 0.5 ; and RR , 0.6 ; 95 % CI , 0.5 to 0.8 , respectively ) , with similar annual rates of major hemorrhage ( 1.0 % and 1.1 % , respectively ) . Conclusions —Women are at higher risk than men for AF-related thromboembolism off warfarin . Warfarin therapy appears be as effective in women , if not more so , than in men , with similar rates of major hemorrhage . Female sex is an independent risk factor for thromboembolism and should influence the decision to use anticoagulant therapy in persons with AF Objective To compare the predictive power of the main existing and recently proposed schemes for stratification of risk of stroke in older patients with atrial fibrillation . Design Comparative cohort study of eight risk stratification scores . Setting Trial of thromboprophylaxis in stroke , the Birmingham Atrial Fibrillation in the Aged ( BAFTA ) trial . Participants 665 patients aged 75 or over with atrial fibrillation based in the community who were r and omised to the BAFTA trial and were not taking warfarin throughout or for part of the study period . Main outcome measures Events rates of stroke and thromboembolism . Results 54 ( 8 % ) patients had an ischaemic stroke , four ( 0.6 % ) had a systemic embolism , and 13 ( 2 % ) had a transient ischaemic attack . The distribution of patients classified into the three risk categories ( low , moderate , high ) was similar across three of the risk stratification scores ( revised CHADS2 , NICE , ACC/AHA/ESC ) , with most patients categorised as high risk ( 65 - 69 % , n=460 - 457 ) and the remaining classified as moderate risk . The original CHADS2 ( Congestive heart failure , Hypertension , Age ≥75 years , Diabetes , previous Stroke ) score identified the lowest number as high risk ( 27 % , n=180 ) . The incremental risk scores of CHADS2 , Rietbrock modified CHADS2 , and CHA2DS2-VASc ( CHA2DS2-Vascular disease , Age 65 - 74 years , Sex ) failed to show an increase in risk at the upper range of scores . The predictive accuracy was similar across the tested schemes with C statistic ranging from 0.55 ( original CHADS2 ) to 0.62 ( Rietbrock modified CHADS2 ) , with all except the original CHADS2 predicting better than chance . Bootstrapped paired comparisons provided no evidence of significant differences between the discriminatory ability of the schemes . Conclusions Based on this single trial population , current risk stratification schemes in older people with atrial fibrillation have only limited ability to predict the risk of stroke . Given the systematic undertreatment of older people with anticoagulation , and the relative safety of warfarin versus aspirin in those aged over 70 , there could be a pragmatic rationale for classifying all patients over 75 as “ high risk ” until better tools are available Background Antithrombotic management in atrial fibrillation ( AF ) is currently based on clinical characteristics , despite evidence of potential fine-tuning with transoesophageal echocardiography ( TEE ) . This open , r and omised , multicentre study addresses the hypothesis that a comprehensive strategy of TEE-based aspirin treatment in AF patients is feasible and safe . Methods Between 2005 and 2009 , ten large hospitals in the Netherl and s enrolled AF patients with a moderate risk of stroke . Patients without thrombogenic TEE characteristics were r and omised to aspirin or vitamin K antagonists ( VKA ) . The primary objective is to show that TEE-based aspirin treatment is safe compared with VKA therapy . The secondary objective tests feasibility of TEE as a tool to detect echocardiographic features of high stroke risk . This report compares r and omised to non-r and omised patients and describes the feasibility of a TEE-based approach . Results In total , 310 patients were included . Sixty-nine patients were not r and omised because of non-visualisation ( n = 6 ) or TEE risk factors ( n = 63 ) . Compared with non-r and omised patients , r and omised patients ( n = 241 ) were younger ( 65 ± 11 vs. 69 ± 9 years , p = 0.004 ) , had less  coronary artery disease ( 9 vs. 20 % , p = 0.018 ) , previous TIA ( 1.7 vs. 7.2 % , p = 0.029 ) , AF during TEE ( 25 vs. 54 % , p < 0.001 ) , mitral incompetence ( 55 vs. 70 % , p = 0.038 ) , VKA use ( 69 vs. 82 % , p = 0.032 ) , had a lower mean CHADS2 score ( 1.2 ± 0.6 vs. 1.6 ± 1.0 , p = 0.004 ) , and left ventricular ejection fraction ( 59 ± 8 vs. 56 ± 8 % , p = 0.016 ) . Conclusions This study shows that a TEE-based approach for fine-tuning stroke risk in AF patients with a moderate risk for stroke is feasible . Follow-up data will address the safety of this TEE-based approach In a prospect i ve study of 312 older patients with chronic atrial fibrillation , at 36-month follow-up evaluation , new thromboembolic stroke developed in 162 of 312 patients ( 52 % ) . Significant independent risk factors for new thromboembolic stroke were prior stroke ( risk ratio = 1.6 ) , rheumatic mitral stenosis ( risk ratio = 2.0 ) , left ventricular ( LV ) hypertrophy ( risk ratio = 2.8 ) , abnormal LV ejection fraction ( risk ratio = 1.8 ) , serum total cholesterol ( risk ratio = 1.005 ) , and serum high-density lipoprotein cholesterol ( risk ratio = 0.96 ) BACKGROUND The use of warfarin reduces the rate of ischemic stroke in patients with atrial fibrillation but requires frequent monitoring and dose adjustment . Rivaroxaban , an oral factor Xa inhibitor , may provide more consistent and predictable anticoagulation than warfarin . METHODS In a double-blind trial , we r and omly assigned 14,264 patients with nonvalvular atrial fibrillation who were at increased risk for stroke to receive either rivaroxaban ( at a daily dose of 20 mg ) or dose-adjusted warfarin . The per- protocol , as-treated primary analysis was design ed to determine whether rivaroxaban was noninferior to warfarin for the primary end point of stroke or systemic embolism . RESULTS In the primary analysis , the primary end point occurred in 188 patients in the rivaroxaban group ( 1.7 % per year ) and in 241 in the warfarin group ( 2.2 % per year ) ( hazard ratio in the rivaroxaban group , 0.79 ; 95 % confidence interval [ CI ] , 0.66 to 0.96 ; P<0.001 for noninferiority ) . In the intention-to-treat analysis , the primary end point occurred in 269 patients in the rivaroxaban group ( 2.1 % per year ) and in 306 patients in the warfarin group ( 2.4 % per year ) ( hazard ratio , 0.88 ; 95 % CI , 0.74 to 1.03 ; P<0.001 for noninferiority ; P=0.12 for superiority ) . Major and nonmajor clinical ly relevant bleeding occurred in 1475 patients in the rivaroxaban group ( 14.9 % per year ) and in 1449 in the warfarin group ( 14.5 % per year ) ( hazard ratio , 1.03 ; 95 % CI , 0.96 to 1.11 ; P=0.44 ) , with significant reductions in intracranial hemorrhage ( 0.5 % vs. 0.7 % , P=0.02 ) and fatal bleeding ( 0.2 % vs. 0.5 % , P=0.003 ) in the rivaroxaban group . CONCLUSIONS In patients with atrial fibrillation , rivaroxaban was noninferior to warfarin for the prevention of stroke or systemic embolism . There was no significant between-group difference in the risk of major bleeding , although intracranial and fatal bleeding occurred less frequently in the rivaroxaban group . ( Funded by Johnson & Johnson and Bayer ; ROCKET AF Clinical Trials.gov number , NCT00403767 . ) BACKGROUND A prothrombotic or hypercoagulable state in atrial fibrillation may contribute to stroke and thromboembolism . Results of longitudinal population -based studies in elderly people with atrial fibrillation are not yet available . METHODS In the Rotterdam Study , a population -based prospect i ve cohort study , 162 participants with atrial fibrillation at baseline , aged 55 years and over , were matched for age and gender with 324 people in sinus rhythm . Associations were examined between three coagulation factors and the risk of total and cardiac mortality and stroke . Hazard rate ratios were calculated with 95 % confidence intervals using Cox 's proportional hazards model , adjusted for potential confounders . RESULTS Plasma von Willebr and factor was , age- and gender-adjusted , associated with cardiac mortality in the total population ( relative risk 1.16 ; 1.06 - 1.27 , per 10 IU dL(-1 ) increase ) , but statistical significance was lost after additional adjustments . A strong association ( 1.27 ; 1.08 - 1.50 , per 5-unit increase ) was found between soluble P-selectin ( sP-sel ) and cardiac mortality in atrial fibrillation patients but not in participants in sinus rhythm . Furthermore , the expected association between fibrinogen and cardiac mortality was observed only in those in sinus rhythm ( 2.60 ; 1.69 - 4.01 , per unit increase ) , and not in atrial fibrillation . No associations were found between coagulation factors and stroke . CONCLUSIONS In this population -based study , plasma levels of sP-sel predicted clinical adverse outcomes in atrial fibrillation , suggesting a role of platelets in the prothrombotic state associated with atrial fibrillation . Fibrinogen was a risk factor of cardiac and all-cause mortality in sinus rhythm , but not in atrial fibrillation Abstract Chronic atrial fibrillation ( AF ) in the presence or absence of rheumatic valvular heart disease is associated with an increased incidence of stroke . 1,2 We reported in a prospect i ve study that at 27-month follow-up , echocardiographic left ventricular ( LV ) hypertrophy in elderly patients with systolic or diastolic hypertension was associated with an increased incidence of new atherothrombotic brain infa rct ion . 3 We also demonstrated in a prospect i ve study that at 3-year follow-up , risk factors for atherothrombotic brain infa rct ion were cigarette smoking , systolic or diastolic hypertension and diabetes mellitus in elderly men and systolic or diastolic hypertension , diabetes mellitus and obesity in elderly women . 4 This report correlates in elderly patients with chronic AF the prevalence of thromboembolic ( TE ) stroke with the presence or absence of rheumatic mitral stenosis , mitral anular calcium , valvular aortic stenosis , systolic or diastolic hypertension , prior myocardial infa rct ion , left atrial enlargement and LV hypertrophy BACKGROUND AND PURPOSE The risk of major vascular events after an initial episode of cerebral ischemia in patients with nonrheumatic atrial fibrillation ( NRAF ) varies from 2 % to 15 % in the first year and is approximately 5 % yearly thereafter . Few studies have reported on risk factors that can be used to identify high-risk subgroups within this patient population . METHODS We studied the predictive value of several easily obtainable clinical characteristics in a group of 375 placebo-treated patients with NRAF and a recent episode of transient or nondisabling cerebral ischemia who were entered in a multicenter clinical trial . The mean follow-up was 1.6 years . RESULTS By means of multivariate modeling , six independent variables were identified : history of previous thromboembolism , ischemic heart disease , enlarged cardiothoracic ratio on chest roentgenogram , systolic blood pressure greater than 160 mm Hg at study entry , NRAF for more than 1 year , and presence of an ischemic lesion on CT scan . These variables could also be used to stratify patients in low- , medium- , and high-risk subgroups for the other two arms of the trial , those treated with anticoagulation and aspirin .  Patients older than 75 years with three or more risk factors seemingly benefited less from both aspirin and anticoagulant treatment . CONCLUSIONS Easily obtainable patient characteristics are helpful in estimating the potential effect of adequate secondary prevention in patients with NRAF who recently suffered a transient ischemic attack or minor ischemic stroke Transesophageal echocardiography visualizes the left atrium and its appendage and is more sensitive than transthoracic echocardiography for diagnosing thrombi of the left atrium and the left atrial appendage and spontaneous echocardiographic contrast of the left atrium [ 1 - 3 ] . The left atrium and especially the left atrial appendage are the presumed sites of thrombus formation and sources of arterial emboli in patients with atrial fibrillation [ 4 ] . Patients with atrial fibrillation and a history of stroke or embolism were shown to have a higher prevalence of thrombi of the left atrium or the left atrial appendage , a higher prevalence of spontaneous echocardiographic contrast , and a larger left atrial appendage than patients with no history of stroke or embolism [ 2 , 5 , 6 ] . However , whether these abnormalities are predictors for stroke or embolism remains controversial [ 7 , 8 ] . Furthermore , no studies have determined whether transesophageal echocardiography helps to assess risk for stroke or embolism in out patients with atrial fibrillation who have no history of stroke or embolism or whether transesophageal echocardiography is useful in the decision to initiate anticoagulation . We therefore performed a prospect i ve , multicenter study of out patients with atrial fibrillation who had not recently had stroke . We sought to determine whether thrombi of the left atrium or the left atrial appendage , spontaneous echocardiographic contrast , and size of the left atrial appendage are associated with stroke or embolism . Our hypothesis was that patients with thrombi of the left atrium or the left atrial appendage , spontaneous echocardiographic contrast , and enlargement of the left atrial appendage have a higher rate of stroke or embolism than do patients without these abnormalities . The baseline clinical and echocardiographic characteristics of our study sample have been reported elsewhere [ 9 ] . Methods Patient Recruitment Our study was conducted in Austria and Slovakia . At the beginning of the study , general practitioners and internists from surrounding participating centers were informed about the study and were asked to refer patients who had constant or intermittent atrial fibrillation . At each patient 's first visit , a cardiologist recorded baseline data , associated illnesses , clinical characteristics ( definitions of which are listed in Appendix 2 ) , and the cause of atrial fibrillation . A 12-lead electrocardiogram was recorded on 2 separate days . We excluded patients with prosthetic valves and those who were already receiving anticoagulation . Current therapy with aspirin was not an exclusion criterion . Patients who had mitral valve stenosis or had recently had stroke were excluded because anticoagulation was indicated for such conditions . For the definition of recent stroke , we chose a cutoff value of 1 year because a previous study reported that the risk for recurrent stroke was increased in patients who had had an ischemic event in the previous year [ 10 ] . Echocardiography For transthoracic echocardiography , 2.5- or 3.5-MHz probes were used . For M-mode measurements , we applied the recommendations of the American Society of Echocardiography [ 11 ] . M-mode measurements were performed on-line and were documented on printouts . Regional wall-motion and valvular abnormalities were recorded . In patients without regional wall-motion abnormalities , left ventricular systolic function was assessed by calculation of left ventricular fractional shortening . For transesophageal echocardiography , biplane 5-MHz probes were used in 64 % of the patients and monoplane 5-MHz probes were used in 36 % . After local anesthesia with lidocaine spray was administered , the probe was introduced into the nonse date d patients , who lay on their left side . The entire study was recorded on S-VHS videotapes . The cardiac chambers and valves were investigated by using all obtainable views [ 12 , 13 ] . Special care was taken to visualize the whole cavity of the left atrium and its appendage from different planes , with the tip of the probe slightly flexed . The size of the left atrial appendage was measured off-line . A frame that best visualized the left atrial appendage with respect to its orifice , extension , and delineation of borders was selected just before the QRS complex . The length of the left atrial appendage was defined as the distance between the limbus of the left superior pulmonary vein and the apex of the left atrial appendage ; the width of the left atrial appendage was defined as the longest distance between the lateral and ventricular left atrial appendage wall , measured in a line perpendicular to the course of the left atrial appendage curvature ; and the left atrial appendage area was defined as described elsewhere [ 14 ] . For the assessment of intra- and interobserver deviations , left atrial appendage size was measured 1 year after the initial measurement in 20 r and omly selected video recordings by the same observer and in 60 r and omly selected video recordings by three observers from different centers . A thrombus of the left atrium or left atrial appendage was considered definite if at least three of the following five criteria were present : clear borders , echogenicity different from that of surrounding structures , independent mobility , longest diameter greater than 15 mm , and evidence of thrombus in more than one imaging plane [ 15 ] . A second observer from a different center review ed video recordings to confirm diagnosis of thrombus of the left atrium or left atrial appendage . A thrombus was considered probable if only two criteria were present or if the observers disagreed . Spontaneous echocardiographic contrast was diagnosed in the presence of dynamic smoke-like echoes within the left atrium or left atrial appendage with a characteristic swirling motion that was distinct from white noise artifact [ 16 ] . When spontaneous echocardiographic contrast was suspected , the gain setting s were decreased in a stepwise manner to exclude artifact caused by excessive gain . The compression and gain controls were then adjusted to ensure the best possible visualization . Spontaneous echocardiographic contrast was not quantified . A second observer from a different center checked the diagnosis of spontaneous echocardiographic contrast by review ing all video recordings . When the observers disagreed about the presence or absence of spontaneous echocardiographic contrast , the decision made at the time of examination was chosen . This was done because spontaneous echocardiographic contrast was not always visible on review of the video recordings . Outcome Events Primary events were stroke and embolism that extended to viscera or extremities . Stroke was defined as acute onset of a focal neurologic deficit that lasted more than 24 hours and was consistent with a vascular event . Severity and subtypes of stroke were assessed according to established criteria [ 17 ] . Embolism extending to viscera or extremities was defined as a sudden onset of pain that was associated with typical findings on Doppler ultrasonography , angiography , surgery , or autopsy . Secondary events were the need for anticoagulation during follow-up in patients who were primarily receiving aspirin and death not caused by stroke or embolism . Death not caused by stroke or embolism was classified as cardiac or noncardiac on the basis of information from the treating physician and the patient 's family . Follow-up Visits took place 3 , 6 , 12 , 18 , and 24 months after study entry . After a follow-up period of at least 2 years ( ending in February 1994 ) , it was evident that the number of primary outcome events was low . We therefore prolonged the follow-up period and planned further visits , one to be held in 1994 and one to be held in 1995 . Patients who were unwilling or unable to attend the visits were contacted by telephone . Medical records were obtained for patients who had been admitted to a hospital . If a patient had died , an autopsy report or death certificate was obtained . Treatment and Ethical Considerations Although our study was design ed to be observational , we recommended antithrombotic treatment to the patients because of ethical considerations . Because patients with thrombi of the left atrium or left atrial appendage are considered to have a high risk for embolism , we recommended that they receive anticoagulation . The target range for the international normalized ratio was 2.0 to 3.0 , and the treating physicians monitored the ratio [ 5 , 18 ] . We recommended that the remaining patients receive aspirin , 160 mg/d , because preliminary data indicated that aspirin reduces the risk for stroke or embolism in patients with atrial fibrillation [ 19 ] . The institutional review board of the participating centers approved the study . Patients were informed about the background and the procedures of the trial , and informed consent was obtained according to the rules of each center . Statistical Analysis For baseline data , group comparisons were done by analysis of variance for normally distributed data and by the nonparametric Kruskal-Wallis test for data that were not normally distributed . If appropriate , we used the Scheffe post hoc test . The Wilk-Shapiro test was used to check for normality . Contingency table methods , including the chi-square test and the Fisher exact test , were used to analyze categorical data . We used the Cox proportional-hazards model to obtain estimates of relative risk and 95 % CIs for all univariate and multivariate analyses of time-to-event data . All tests were two-sided . The level of significance assumed was an level of 0.05 . We used SAS software ( SAS Institute , Cary , North Carolina ) for analyses . Role of Funding Sources The funding sources had no role in the collection , analysis , or interpretation of the data ; did not review the manuscript at any time ; and were not involved in su bmi tting the paper for publication . Results Patients Patients were recruited between January 1990 and February 1992 . Of the 474 PURPOSE R and omized controlled trials have demonstrated that anticoagulant therapy is very effective at preventing stroke among patients with nonrheumatic atrial fibrillation . However , these trials have reported too few strokes for powerful risk factor analysis . Observational studies may provide additional information . The purpose of this study was to identify risk factors in a larger number of patients with stroke and nonrheumatic atrial fibrillation , using case-control methodology . PATIENTS AND METHODS We identified all patients discharged from one hospital over an 8-year period who met our case definition of nonrheumatic atrial fibrillation and ischemic stroke ( n = 134 ) , and compared them with contemporaneous control subjects who were discharged with nonrheumatic atrial fibrillation without stroke ( n = 131 ) . RESULTS Cases and controls were similar in terms of duration of atrial fibrillation ; proportion with paroxysmal atrial fibrillation ; percentage with a past medical history of angina , myocardial infa rct ion , congestive heart failure , diabetes , or smoking ; and mean left atrial size . In contrast , cases were significantly older than controls ( 78.5 versus 74.8 years , p = 0.002 ) and more likely to have a history of hypertension ( 55 % versus 38 % , p = 0.0093 ) . The relative odds for stroke was 1.91 for patients with hypertension , 1.73 for patients older than 75 years , and 3.26 for patients with both factors . CONCLUSIONS Our analysis suggests that age and hypertension should be considered when deciding upon long-term anticoagulant therapy to prevent stroke in patients with nonrheumatic atrial fibrillation BACKGROUND The presence of vascular disease ( peripheral artery disease [ PAD ] and /or myocardial infa rct ion [ MI ] ) may impact on the risk of stroke and death among patients with incident atrial fibrillation ( AF ) . To test this hypothesis , we analyzed data from a large Danish prospect i ve cohort , the Danish Diet , Cancer and Health ( DCH ) study , to assess the risk of stroke or death among those who developed AF according to concomitant presence of vascular disease . METHODS A prospect i ve cohort study of 57 , 053 persons ( 27 , 178 men and 29 , 876 women , respectively ) , aged between 50 and 64 years . The risk of stroke or death for patients with vascular disease was assessed amongst 3315 patients with incident AF ( mean age , 67.1years ; 2130 men , 1185 women ) using Cox proportional hazard models , after a median follow-up of 4.8 years . RESULTS Of the subjects with AF , 417 ( 12.6 % ) had ' vascular disease ' ( PAD and /or prior MI ) . The risk of the primary endpoint ( stroke or death ) was significantly higher in patients with vascular disease at 1-year follow-up ( crude hazard ratio [ HR ] 2.51 [ 1.91 - 3.29 ] ) , with corresponding crude HRs for PAD and MI being 3.51 ( 2.40 - 5.13 ) , and 1.99 ( 1.46 - 2.72 ) , respectively . For the secondary endpoints of death or stroke individually , these risk estimates were similar ( crude HR 2.48 [ 1.89 - 3.26 ] and 1.77 [ 1.18 - 2.66 ] , respectively ) . After adjustment for risk factors within the CHADS(2 ) score , the adjusted HR for the primary endpoint ( stroke or death ) in patients with vascular disease was 1.91 ( 1.44 - 2.54 ) , which was also significant for death ( 1.97 [ 1.48 - 2.62 ] ) . CONCLUSION Vascular disease ( prior MI and PAD ) is an independent risk factor for the primary endpoint of ' stroke or death ' in patients with AF , even after adjustment for the CHADS(2 ) risk score , although this is driven by the impact on mortality . This reaffirms that patients with vascular disease represent a ' high-risk ' population , which necessitates proactive management of all cardiovascular risk factors and effective thromboprophylaxis ( i.e. oral anticoagulation ) , which has been shown to significantly reduce the risk of stroke and death in AF BACKGROUND Anticoagulants are more effective than antiplatelet agents at reducing stroke risk in patients with atrial fibrillation , but whether this benefit outweighs the increased risk of bleeding in elderly patients is unknown . We assessed whether warfarin reduced risk of major stroke , arterial embolism , or other intracranial haemorrhage compared with aspirin in elderly patients . METHODS 973 patients aged 75 years or over ( mean age 81.5 years , SD 4.2 ) with atrial fibrillation were recruited from primary care and r and omly assigned to warfarin ( target international normalised ratio 2 - 3 ) or aspirin ( 75 mg per day ) . Follow-up was for a mean of 2.7 years ( SD 1.2 ) . The primary endpoint was fatal or disabling stroke ( ischaemic or haemorrhagic ) , intracranial haemorrhage , or clinical ly significant arterial embolism . Analysis was by intention to treat . This study is registered as an International St and ard R and omised Controlled Trial , number IS RCT N89345269 . FINDINGS There were 24 primary events ( 21 strokes , two other intracranial haemorrhages , and one systemic embolus ) in people assigned to warfarin and 48 primary events ( 44 strokes , one other intracranial haemorrhage , and three systemic emboli ) in people assigned to aspirin ( yearly risk 1.8%vs 3.8 % , relative risk 0.48 , 95 % CI 0.28 - 0.80 , p=0.003 ; absolute yearly risk reduction 2 % , 95 % CI 0.7 - 3.2 ) . Yearly risk of extracranial haemorrhage was 1.4 % ( warfarin ) versus 1.6 % ( aspirin ) ( relative risk 0.87 , 0.43 - 1.73 ; absolute risk reduction 0.2 % , -0.7 to 1.2 ) . INTERPRETATION These data support the use of anticoagulation therapy for people aged over 75 who have atrial fibrillation , unless there are contraindications or the patient decides that the benefits are not worth the inconvenience OBJECTIVE To examine the cost-effectiveness of prescribing warfarin sodium in patients who have nonvalvular atrial fibrillation ( NVAF ) with or without additional stroke risk factors ( a prior stroke or transient ischemic attack , diabetes , hypertension , or heart disease ) . DESIGN Decision and cost-effectiveness analyses . The probabilities for stroke , hemorrhage , and death were obtained from published r and omized controlled trials . The quality -of-life estimates were obtained by interviewing 74 patients with atrial fibrillation .  Costs were estimated from literature review , phone survey , and Medicare reimbursement . PATIENTS In the base case , the patients were 65 years of age and good c and i date s for warfarin therapy . INTERVENTIONS Treatment with warfarin , aspirin , or no therapy in the decision analytic model . MAIN OUTCOME MEASURES Quality -adjusted survival and marginal cost-effectiveness of warfarin  as compared with  aspirin  or no therapy . RESULTS For patients with NVAF and additional risk factors for stroke , warfarin therapy led to a greater quality -adjusted survival and to cost savings . For patients with NVAF and one additional risk factor , warfarin therapy cost $ 8000 per quality -adjusted life-year saved . For 65-year-old patients with NVAF alone , warfarin cost about $ 370,000 per quality -adjusted life-year saved , as compared with aspirin therapy . However , for 75-year-old patients with NVAF alone , prescribing warfarin cost $ 110,000 per quality -adjusted life-year saved . For patients who were not prescribed warfarin , aspirin was preferred to no therapy on the basis of both quality -adjusted survival and cost in all patients , regardless of the number of risk factors present . CONCLUSIONS Treatment with warfarin is cost-effective in patients with NVAF and one or more additional risk factors for stroke . In 65-year-old patients with NVAF but no other risk factors for stroke , prescribing warfarin instead of aspirin would affect quality -adjusted survival minimally but increase costs significantly BACKGROUND Clinical features that consistently predict ischemic stroke in patients with nonvalvular atrial fibrillation have been identified , while echocardiographic risk factors are less well defined . OBJECTIVE To determine whether the results of transthoracic echocardiography add independent information to the clinical risk factors for stroke in patients with atrial fibrillation . METHODS Transthoracic echocardiographic findings and clinical features from 1066 patients with atrial fibrillation assigned to placebo or control in 3 r and omized trials ( Boston Area Anticoagulation Trial for Atrial Fibrillation , Stroke Prevention in Atrial Fibrillation I Study , and Veterans Affairs Prevention in Atrial Fibrillation Study ) were correlated with subsequent ischemic stroke by multivariate analysis . RESULTS The mean + SD age of patients was 67 + /- 10 years , 78 % were men , 55 % had a history of hypertension , 19 % had a history of diabetes , 7 % had a previous transient ischemic attack or stroke , and 27 % had a history of heart failure . During a mean follow-up of 1.6 years , 78 ischemic strokes occurred ( annual rate , 4.7 % ) . Moderate to severe left ventricular systolic dysfunction shown via 2-dimensional echocardiography was a strong independent predictor of stroke ( relative risk , 2.5 ; P<.001 ) in the 1010 patients in whom echocardiographic values for left ventricular function were available . Left atrial diameter by M-mode echocardiography did not predict stroke ( relative risk , 1.02/mm ; P = .10 ) . Of 163 patients categorized as low risk based on clinical features ( annual stroke rate , 0.8 % ; 95 % confidence interval , 0.2%-3.0 % ) , 10 had moderate to severe left ventricular dysfunction shown via 2-dimensional echocardiography and a 9.3 % per year risk of stroke ( 95 % confidence interval , 1.3%-66 % ) . Conversely , 728 of the 847 patients at high risk for stroke based on clinical criteria had normal or mildly abnormal left ventricular function ; their stroke rate was 4.4 % ( 95 % confidence interval , 3.4%-5.8 % ) . CONCLUSIONS Left ventricular systolic dysfunction shown via 2-dimensional transthoracic echocardiography independently predicts risk of stroke in patients with atrial fibrillation . Echocardiography may prove most useful in a small group of patients who have a low risk of stroke according to clinical factors CONTEXT Warfarin has been shown to be highly efficacious for preventing  thromboembolism in atrial fibrillation in r and omized trials , but its effectiveness and safety in clinical practice is less clear . OBJECTIVE To evaluate the effect of warfarin on risk of thromboembolism , hemorrhage , and death in atrial fibrillation within a usual care setting . DESIGN Cohort study assembled between July 1 , 1996 , and December 31 , 1997 , and followed up through August 31 , 1999 . SETTING Large integrated health care system in Northern California . PATIENTS Of 13,559 adults with nonvalvular atrial fibrillation , 11,526 were studied , 43 % of whom were women , mean age 71 years , with no known contraindications to anticoagulation at baseline . MAIN OUTCOMES Ischemic stroke , peripheral embolism , hemorrhage , and death according to warfarin use and comorbidity status , as determined by automated data bases , review of medical records , and state mortality files . RESULTS Among 11,526 patients , 397 incident thromboembolic events ( 372 ischemic strokes , 25 peripheral embolism ) occurred during 25,341 person-years of follow-up , and warfarin therapy was associated with a 51 % ( 95 % confidence interval [ CI ] , 39%-60 % ) lower risk of thromboembolism compared with no warfarin therapy ( either no antithrombotic therapy or aspirin ) after adjusting for potential confounders and likelihood of receiving warfarin . Warfarin was effective in reducing thromboembolic risk in the presence or absence of risk factors for stroke . A nested case-control analysis estimated a 64 % reduction in odds of thromboembolism with warfarin compared with no antithrombotic therapy . Warfarin was also associated with a reduced risk of all-cause mortality ( adjusted hazard ratio , 0.69 ; 95 % CI , 0.61 - 0.77 ) . Intracranial hemorrhage was uncommon , but the rate was moderately higher among those taking vs those not taking warfarin ( 0.46 vs 0.23 per 100 person-years , respectively ; P = .003 , adjusted hazard ratio , 1.97 ; 95 % CI , 1.24 - 3.13 ) . However , warfarin therapy was not associated with an increased adjusted risk of nonintracranial major hemorrhage . The effects of warfarin were similar when patients with contraindications at baseline were analyzed separately or combined with those without contraindications ( total cohort of 13,559 ) . CONCLUSIONS Warfarin is very effective for preventing ischemic stroke in patients with atrial fibrillation in clinical practice while the absolute increase in the risk of intracranial hemorrhage is small . Results of r and omized trials of anticoagulation translate well into clinical care for patients with atrial fibrillation AIMS We aim ed to investigate the prevalence and incidence of atrial fibrillation ( AF )  in a large European population -based study . METHODS AND RESULTS The study is part of the Rotterdam study , a population -based prospect i ve cohort study among subjects aged 55 years and above . The prevalence at baseline was assessed in 6808 participants .  Incidence of AF was investigated during a mean follow-up period of 6.9 years in 6432 persons . We identified 376 prevalent and 437 incident cases . Overall prevalence was 5.5 % , rising from 0.7 % in the age group 55 - 59 years to 17.8 % in those aged 85 years and above . The overall incidence rate was 9.9/1000 person-years . The incidence rate in the age group 55 - 59 years was 1.1/1000 person-years , rose to 20.7/1000 person-years in the age group 80 - 84 years and stabilized in those aged 85 years and above . Prevalence and incidence were higher in men than in women . The lifetime risk to develop AF at the age of 55 years was 23.8 % in men and 22.2 % in women . CONCLUSION In this prospect i ve study in a European population , the prevalence and incidence of AF increased with age and were higher in men than in women . The high lifetime risk to develop AF was similar to North American epidemiological data BACKGROUND Warfarin reduces the risk for ischemic stroke in patients with atrial fibrillation ( AF ) but increases the risk for hemorrhage . Dabigatran is a fixed-dose , oral direct thrombin inhibitor with similar or reduced rates of ischemic stroke and intracranial hemorrhage in patients with AF compared with those of warfarin . OBJECTIVE To estimate the quality -adjusted survival , costs , and cost-effectiveness of dabigatran compared with adjusted-dose warfarin for preventing ischemic stroke in patients 65 years or older with nonvalvular AF . DESIGN Markov decision model . DATA SOURCES The RE-LY ( R and omized Evaluation of Long-Term Anticoagulation Therapy ) trial and other published studies of anticoagulation . The cost of dabigatran was estimated on the basis of pricing in the United Kingdom . TARGET POPULATION Patients aged 65 years or older with nonvalvular AF and risk factors for stroke ( CHADS₂ score ≥1 or equivalent ) and no contraindications to anticoagulation . TIME HORIZON Lifetime . PERSPECTIVE Societal . INTERVENTION Warfarin anticoagulation ( target international normalized ratio , 2.0 to 3.0 ) ; dabigatran , 110 mg twice daily ( low dose ) ; and dabigatran , 150 mg twice daily ( high dose ) . OUTCOME MEASURES Quality -adjusted life-years ( QALYs ) , costs ( in 2008 U.S. dollars ) , and incremental cost-effectiveness ratios . RESULTS OF BASE-CASE ANALYSIS The quality -adjusted life expectancy was 10.28 QALYs with warfarin , 10.70 QALYs with low-dose dabigatran , and 10.84 QALYs with high-dose dabigatran . Total costs were $ 143 193 for warfarin , $ 164 576 for low-dose dabigatran , and $ 168 398 for high-dose dabigatran . The incremental cost-effectiveness ratios  compared with warfarin were $ 51 229 per QALY for low-dose dabigatran and $ 45 372 per QALY for high-dose dabigatran . RESULTS OF SENSITIVITY ANALYSIS The model was sensitive to the cost of dabigatran but was relatively insensitive to other model inputs . The incremental cost-effectiveness ratio increased to $ 50 000 per QALY at a cost of $ 13.70 per day for high-dose dabigatran but remained less than $ 85 000 per QALY over the full range of model inputs evaluated . The cost-effectiveness of high-dose dabigatran improved with increasing risk for stroke and intracranial hemorrhage . LIMITATION Event rates were largely derived from a single r and omized clinical trial and extrapolated to a 35-year time frame from clinical trials with approximately 2-year follow-up . CONCLUSION In patients aged 65 years or older with nonvalvular AF at increased risk for stroke ( CHADS₂ score ≥1 or equivalent ) , dabigatran may be a cost-effective alternative to warfarin depending on pricing in the United States . PRIMARY FUNDING SOURCE American Heart Association and Veterans Affairs Health Services Research & Development Service BACKGROUND AND PURPOSE Previous cost-effectiveness analyses analyzed warfarin for stroke prevention in r and omized trial setting s. Given the complexities of warfarin treatment , cost-effectiveness should be examined within a real-world setting . METHODS Our model followed patients with atrial fibrillation at moderate to high risk of stroke through primary and recurrent ischemic stroke , hemorrhages -- intracranial and extracranial , and the result ing disability . Four scenarios were examined : ( 1 ) all patients start on warfarin with perfect control , that is , international normalized ratio ( INR ) values always within range ; ( 2 ) all patients start on warfarin with trial-like control , where INR can fall outside the recommended range ; ( 3 ) all patients start on warfarin with real-world INR control ; and ( 4 ) real-world prescription ( and control ) of warfarin , aspirin , or neither for warfarin-eligible patients . Reported warfarin discontinuation rates were used . Main outcomes were total number of events , quality adjusted life years , and costs in a US setting . RESULTS The total number of primary and recurrent ischemic strokes in a 1,000-patient cohort ( age 70 years , lifetime analysis ) was 626 , 832 , 984 , and 1,171 in scenarios 1 to 4 , respectively . The corresponding mean quality adjusted life years per patient were 7.21 , 6.92 , 6.75 , and 6.67 for scenarios 1 to 4 , respectively . Costs per patient were $ 68,039 , $ 77,764 , $ 84,518 , and $ 87,248 in scenarios 1 to 4 , respectively . If " perfect " adherence to warfarin was assumed , except for discontinuations for clinical reasons , strokes would decrease to 503 , 737 , 909 , and 1,120 in scenarios 1 to 4 , respectively . CONCLUSIONS Clinical and cost outcomes are strongly dependent on the quality of anticoagulation and rates of warfarin discontinuation . Clinicians should work to improve both . Policy makers should use real-world INR control and warfarin discontinuation rates when assessing cost-effectiveness As previously reported , 1007 patients with chronic atrial fibrillation participated in the Copenhagen AFASAK study . Before inclusion to trial , they all had a physical examination , chest roentgenogram , and echocardiogram with determination of left atrial size . This study evaluated the importance of cardiovascular risk factors for development of thromboembolic complications . To exclude any treatment effects on occurrence of thromboembolic complications , we included only the 336 patients from the placebo group . Using Cox 's regression model , previous myocardial infa rct ion was a significant risk factor for development of thromboembolic complications . Age , gender , heart failure , chest pain , hypertensive heart disease , diabetes , systolic and diastolic blood pressure , smoking , relative heart volume , and left atrial size were all without statistical importance PURPOSE The risk of ischemic stroke varies widely among patients with nonvalvular atrial fibrillation , influencing the choice of prophylactic antithrombotic therapy . We assessed three schemes for stroke risk stratification in these patients who were treated with aspirin and who did not have prior cerebral ischemia . SUBJECTS AND METHODS Criteria from three schemes of risk stratification were applied to a longitudinally observed cohort of patients with atrial fibrillation who did not have prior cerebral ischemia and who were treated with aspirin alone or aspirin combined with low , ineffective doses of warfarin in a multicenter clinical trial . The ability of the schemes to identify patients at high ( > /=6 % ) , low ( < /=2 % ) , and intermediate annual risks of ischemic stroke was assessed . RESULTS During a mean follow-up of 1.8 years , 48 ischemic strokes occurred among 1,073 patients with atrial fibrillation who were taking aspirin ( rate = 2.5 per 100 person-years ) . Each of the three schemes predicted stroke and disabling stroke , and successfully identified patients at low risk ( observed stroke rates of 0.3 to 1.1 per 100 person-years ) , although the fractions of the cohort that were categorized as low risk varied from 14 % to 45 % . The observed rates of ischemic stroke among patients categorized as high risk ranged from 3.5 to 7.2 per 100 person-years among the stratification schemes . Two schemes considered all patients > 75 years old as high risk ( observed stroke rate 4.2 per 100 person-years ) , while the remaining scheme classified one third of patients in this age group as low risk ( observed stroke rate 0.6 per 100 person-years ) . CONCLUSIONS When tested in a large cohort of patients with atrial fibrillation who were treated with aspirin  , available risk-stratification schemes successfully identified patients with low rates of ischemic stroke , but less consistently identified high-risk patients OBJECTIVES The purpose of this study was to investigate predictors of bleeding in a cohort of anticoagulated patients and to evaluate the predictive value of several bleeding risk stratification schemas . BACKGROUND The risk of bleeding during antithrombotic therapy in patients with atrial fibrillation ( AF ) is not homogeneous , and several clinical risk factors have been incorporated into clinical bleeding risk stratification schemas . Current risk stratification schemas for bleeding during anticoagulation therapy have been based on complex scoring systems that are difficult to apply in clinical practice , and few have been derived and vali date d in AF cohorts . METHODS We investigated predictors of bleeding in a cohort of 7,329 patients with AF participating in the SPORTIF ( Stroke Prevention Using an ORal Thrombin Inhibitor in Atrial Fibrillation ) III and V clinical trials and evaluated the predictive value of several risk stratification schemas by multivariate analysis . Patients were anticoagulated orally with either adjusted-dose warfarin ( target international normalized ratio 2 to 3 ) or fixed-dose ximelagatran 36 mg twice daily . Major bleeding was central ly adjudicated , and concurrent aspirin therapy was allowed in patients with clinical atherosclerosis . RESULTS By multivariate analyses , significant predictors of bleeding were concurrent aspirin use ( hazard ratio [ HR ] : 2.10 ; 95 % confidence interval [ CI ] : 1.59 to 2.77 ; p < 0.001 ) ; renal impairment ( HR : 1.98 ; 95 % CI : 1.42 to 2.76 ; p < 0.001 ) ; age 75 years or older ( HR : 1.63 ; 95 % CI : 1.23 to 2.17 ; p = 0.0008 ) ; diabetes ( HR : 1.47 ; 95 % CI : 1.10 to 1.97 ; p = 0.009 ) , and heart failure or left ventricular dysfunction ( HR : 1.32 ; 95 % CI : 1.01 to 1.73 ; p = 0.041 ) . Of the tested schemas , the new HAS-BLED ( Hypertension , Abnormal Renal/Liver Function , Stroke , Bleeding History or Predisposition , Labile INR , Elderly , Drugs/Alcohol Concomitantly ) score performed best , with a stepwise increase in rates of major bleeding with increasing HAS-BLED score ( p(trend ) < 0.0001 ) . The c statistic for bleeding varied between 0.50 and 0.67 in the overall entire cohort and 0.68 among patients naive to warfarin at baseline ( n = 769 ) . CONCLUSIONS This analysis identifies diabetes and heart failure or left ventricular dysfunction as potential risk factors for bleeding in AF beyond those previously recognized . Of the contemporary bleeding risk stratification schemas , the new HAS-BLED scheme offers useful predictive capacity for bleeding over previously published schemas and may be simpler to apply
target: The various risk stratification schemes classified variable proportions as low , moderate and high risk , but the CHA(2)DS(2)-VASc score classified the smallest proportion of patients as ' low risk ' .
  Anticoagulation with vitamin K antagonists and dabigatran is cost-effective in patients at high risk of stroke , but not in patients without any other stroke risk factor beside AF .
background: nan