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. Assessment of three schemes for stratifying stroke risk in patients with nonvalvular atrial fibrillation. Patients with nonvalvular atrial fibrillation at low risk of stroke during treatment with aspirin: Stroke Prevention in Atrial Fibrillation III Study. The SPAF III Writing Committee for the Stroke Prevention in Atrial Fibrillation Investigators. Warfarin versus aspirin for prevention of thromboembolism in atrial fibrillation: Stroke Prevention in Atrial Fibrillation II Study Impact of a patient decision aid on care among patients with nonvalvular atrial fibrillation: a cluster randomized trial Anticoagulation therapy for stroke prevention in atrial fibrillation: how well do randomized trials translate into clinical practice? Effect of Age on Stroke Prevention Therapy in Patients With Atrial Fibrillation: The Atrial Fibrillation Investigators RISK OF STROKE IN NON-RHEUMATIC ATRIAL FIBRILLATION Adverse outcomes and predictors of underuse of antithrombotic therapy in medicare beneficiaries with chronic atrial fibrillation. Ximelagatran vs warfarin for stroke prevention in patients with nonvalvular atrial fibrillation: a randomized trial. Warfarin for atrial fibrillation. The patient's perspective. Predictors of thromboembolism in atrial fibrillation: II. Echocardiographic features of patients at risk. The Stroke Prevention in Atrial Fibrillation Investigators. Prognostic implications of left atrial spontaneous echo contrast in nonvalvular atrial fibrillation. Antithrombotic Treatment Patterns in Patients with Newly Diagnosed Nonvalvular Atrial Fibrillation: The GLORIA-AF Registry, Phase II. A randomized trial to assess the impact of an antithrombotic decision aid in patients with nonvalvular atrial fibrillation: the DAAFI trial protocol [ISRCTN14429643] Potentially Preventable Strokes in High-Risk Patients With Atrial Fibrillation Who Are Not Adequately Anticoagulated Differences between perspectives of physicians and patients on anticoagulation in patients with atrial fibrillation: observational study. Comorbidity associated with atrial fibrillation: a general practice-based study. Cost-effectiveness of warfarin and aspirin for prophylaxis of stroke in patients with nonvalvular atrial fibrillation. Transesophageal echocardiographic correlates of thromboembolism in high-risk patients with nonvalvular atrial fibrillation. The Stroke Prevention in Atrial Fibrillation Investigators Committee on Echocardiography. Prediction of stroke or TIA in patients without atrial fibrillation using CHADS2 and CHA2DS2-VASc scores Analysis of Stroke in ATHENA: A Placebo-Controlled, Double-Blind, Parallel-Arm Trial to Assess the Efficacy of Dronedarone 400 mg BID for the Prevention of Cardiovascular Hospitalization or Death From Any Cause in Patients With Atrial Fibrillation/Atrial Flutter UKPDS 60: Risk of Stroke in Type 2 Diabetes Estimated by the UK Prospective Diabetes Study Risk Engine
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 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 CONTEXT Nonvalvular atrial fibrillation ( AF ) carries an increased risk for stroke , but absolute rates of stroke vary widely within the broad spectrum of AF patients . OBJECTIVE To prospect ively vali date a risk stratification scheme identifying patients with AF with low rates of stroke when given aspirin .  DESIGN Prospect i ve cohort study with mean duration of follow-up of 2.0 years , conducted between 1993 and 1997 . SETTING Outpatient clinics affiliated with academic medical centers . PATIENTS Patients with AF categorized as " low risk " based on the absence of 4 prespecified thromboembolic risk factors : recent congestive heart failure or left ventricular fractional shortening of 25 % or less , previous thromboembolism , systolic blood pressure greater than 160 mm Hg , or female sex at age older than 75 years . INTERVENTION All participants given aspirin , 325 mg/d . MAIN OUTCOME MEASURES Ischemic stroke ( considered disabling when Rankin score was II or worse 1 - 3 months later ) and systemic embolism ( primary events ) . RESULTS Among 892 participants , the mean ( SD ) age was 67 ( 10 ) years , 78 % were men , and histories of hypertension , diabetes , and ischemic heart disease were present in 46 % , 13 % , and 16 % , respectively . The rate of primary events was 2.2 % per year ( 95 % confidence interval [ CI ] , 1.6%-3.0 % ) , of ischemic stroke was 2.0 % per year ( 95 % CI , 1.5%-2.8 % ) , and of disabling ischemic strokes was 0.8 % per year ( 95 % CI , 0.5%-1.3 % ) . Those with a history of hypertension had a higher rate of primary events ( 3.6 % per year ) than those with no history of hypertension ( 1.1 % per year ) ( P<.001 ) . The rate of disabling ischemic stroke was low in those with and without a history of hypertension ( 1.4 % per year and 0.5 % per year , respectively ) . The rate of major bleeding during aspirin therapy was 0.5 % per year . CONCLUSION Patients with AF who have relatively low rates of ischemic stroke , particularly disabling stroke , during treatment with aspirin can be reliably identified Warfarin is an established treatment for prevention of ischaemic stroke in patients with atrial fibrillation , but the value of this agent relative to aspirin in unclear . In the first Stroke Prevention in Atrial Fibrillation ( SPAF-I ) study , direct comparison of warfarin with aspirin was limited by the small number of thromboembolic events . SPAF-II aims to address this issue and also to assess the differential effects of the two treatments according to age . We compared warfarin ( prothrombin time ratio 1.3 - 1.8 , international normalised ratio 2.0 - 4.5 ) with aspirin 325 mg daily for prevention of ischaemic stroke and systemic embolism ( primary events ) in two parallel r and omised trials involving 715 patients aged 75 years or less and 385 patients older than 75 ; we sought reductions in the absolute rate of primary events by warfarin compared with aspirin of 2 % per year and 4 % per year , respectively . In the younger patients , warfarin decreased the absolute rate of primary events by 0.7 % per year ( 95 % CI-0.4 to 1.7 ) . The primary event rate per year was 1.3 % with warfarin and 1.9 % with aspirin ( relative risk [ RR ] 0.67 , p = 0.24 ) . The absolute rate of primary events in low-risk younger patients ( without hypertension , recent heart failure , or previous thromboembolism ) on aspirin was 0.5 % per year ( 95 % CI 0.1 to 1.9 ) . Among older patients , warfarin decreased the absolute rate of primary events by 1.2 % per year ( 95 % CI-1.7 to 4.1 ) . The primary event rate per year was 3.6 % with warfarin and 4.8 % with aspirin ( RR 0.73 , p = 0.39 ) . In this older group , the rate of all stroke with residual deficit ( ischaemic or haemorrhagic ) was 4.3 % per year with aspirin and 4.6 % per year with warfarin ( RR 1.1 ) . Warfarin may be more effective than aspirin for prevention of ischaemic stroke in patients with atrial fibrillation , but the absolute reduction in stroke rate by warfarin is small . Younger patients without risk factors had a low rate of stroke when treated with aspirin . In older patients the rate of stroke ( ischaemic and haemorrhagic ) was substantial , irrespective of which agent was given . Patient age and the inherent risk of thromboembolism should be considered in the choice of antithrombotic prophylaxis for patients with atrial fibrillation Background : Too few patients with nonvalvular atrial fibrillation ( NVAF ) receive appropriate antithrombotic therapy . We tested the short-term ( primary outcome ) and long-term ( secondary outcome ) effect of a patient decision aid on the appropriateness of antithrombotic therapy among patients with NVAF . Methods : We conducted a cluster r and omized trial with blinded outcome assessment involving 434 NVAF patients from 102 community-based primary care practice s. Patients in the intervention group received a self-administered booklet and audiotape decision aid tailored to their personal stroke risk profile . Patients in the control group received usual care . The primary outcome measure was change in antithrombotic therapy at 3 months . Appropriateness of therapy was defined using the American College of Chest Physicians ( ACCP ) recommendations . Results : The mean patient age was 72 years , and the median duration of NVAF was 5 years . In the control group , there was a 3 % decrease over 3 months in the number of patients receiving therapy appropriate to their risk of stroke ( 40 % [ 85/215 ] at baseline v. 37 % [ 79/215 ] at 3 months ) . In the intervention group , the number of patients receiving therapy appropriate to their stroke risk increased by 9 % ( 32 % [ 69/219 ] at baseline v. 41 % [ 89/219 ] at 3 months ) . Although the proportion of patients whose therapy met the ACCP treatment recommendations did not differ between study arms at baseline ( p = 0.11 ) or 3 months ( p = 0.44 ) , there was a 12 % absolute improvement in the number of patients receiving appropriate care in the intervention group compared with the control group at 3 months ( p = 0.03 ) . The beneficial effect of the decision aid did not persist ( p = 0.44 for differences between study arms after 12 months ) . Interpretation : There was short-term improvement in the appropriateness of antithrombotic care among patients with NVAF who were exposed to a decision aid , but the improvement did not persist 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 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 Estimates of the risk of stroke for men with non-rheumatic atrial fibrillation were obtained from two large cohort studies --the Whitehall Study of London Civil Servants and the British  Regional Heart Study . The first cohort provided an estimated relative risk of stroke of 6.9 compared with controls . This increased risk confirms that of the other prospect i ve estimate , 5.6 , found in the Framingham study . In the second cohort only one of the men at risk had a stroke , and the risk estimate did not differ significantly from unity . The absolute rates of stroke in both cohorts were lower than those reported in the Framingham study , implying a lesser potential benefit from preventive measures . These lower rates should be considered in the planning of trials . The risk of stroke was significantly associated with raised systolic or diastolic blood pressure but not with age or coronary heart disease BACKGROUND AND PURPOSE Antithrombotic therapy can prevent strokes and transient ischemic attacks ( TIAs ) in carefully selected patients who have chronic nonvalvular atrial fibrillation ( NVAF ) . Our objectives were 3-fold : to document the use of warfarin and aspirin therapy in Missouri Medicare beneficiaries with chronic NVAF ; to identify factors associated with warfarin and aspirin underuse ; and to determine the association between prescription of warfarin and aspirin at hospital discharge and adverse outcomes in this elderly , frail population . METHODS We linked chart review s from all Missouri hospitals to Medicare cl aims data from 1993 to 1996 . From chart review s , we documented Medicare beneficiaries ' demographic factors , comorbid conditions , and antithrombotic therapy prescribed at the time of hospital discharge . From Medicare cl aims , we determined the date of outcomes -death from any cause or hospitalization for an ischemic event ( a stroke , a TIA , or a myocardial infa rct ion ) . RESULTS Only 328 ( 55 % ) of the 597 Medicare beneficiaries were prescribed antithrombotic therapy at hospital discharge : 34 % received warfarin and 21 % received aspirin . Advanced age , female gender , and rural residency predicted underuse of antithrombotic therapy . After controlling for these factors , as well as stroke risk factors and contraindications to anticoagulation , the prescription of warfarin was associated with a 24 % relative risk reduction ( RRR ) in adverse outcomes ( P=0.003 ) . Prescription of aspirin was associated with a nonsignificant 5 % RRR in these events ( P=0.56 ) . CONCLUSIONS The underuse of antithrombotic therapy in Medicare beneficiaries who have NVAF is associated with measurable adverse outcomes . The benefit of warfarin therapy may extend to frail , elderly patients , a group that was excluded from r and omized controlled trials . The role of antiplatelet therapy in this population deserves further study because many of these patients have relative contraindications to warfarin CONTEXT In patients with nonvalvular atrial fibrillation , warfarin prevents ischemic stroke , but dose adjustment , coagulation monitoring , and bleeding limit its use . OBJECTIVE To compare the efficacy of the oral direct thrombin inhibitor ximelagatran with warfarin for prevention of stroke and systemic embolism . DESIGN , SETTING , AND PARTICIPANTS Double-blind , r and omized , multicenter trial ( 2000 - 2001 ) conducted at 409 North American sites , involving 3922 patients with nonvalvular atrial fibrillation and additional stroke risk factors . INTERVENTIONS Adjusted-dose warfarin ( aim ing for an international normalized ratio [ INR ] 2.0 to 3.0 ) or fixed-dose oral ximelagatran , 36 mg twice daily . MAIN OUTCOME MEASURES The primary end point was all strokes ( ischemic or hemorrhagic ) and systemic embolic events . The primary analysis was based on demonstrating noninferiority within an absolute margin of 2.0 % per year according to the intention-to-treat model . RESULTS During 6405 patient-years ( mean 20 months ) of follow-up , 88 patients experienced primary events . The mean ( SD ) INR with warfarin ( 2.4 [ 0.8 ] ) was within target during 68 % of the treatment period . The primary event rate with ximelagatran was 1.6 % per year and with warfarin was 1.2 % per year ( absolute difference , 0.45 % per year ; 95 % confidence interval , -0.13 % to 1.03 % per year ; P<.001 for the predefined noninferiority hypothesis ) . When all-cause mortality was included in addition to stroke and systemic embolic events , the rate difference was 0.10 % per year ( 95 % confidence interval , -0.97 % to 1.2 % per year ; P = .86 ) . There was no difference between treatment groups in rates of major bleeding , but total bleeding ( major and minor ) was lower with ximelagatran ( 37 % vs 47 % per year ; 95 % confidence interval for the difference , -14 % to -6.0 % per year ; P<.001 ) . Serum alanine aminotransferase levels rose to greater than 3 times the upper limit of normal in 6.0 % of patients treated with ximelagatran , usually within 6 months and typically declined whether or not treatment continued ; however , one case of documented fatal liver disease and one other suggestive case occurred . CONCLUSIONS The results establish the efficacy of fixed-dose oral ximelagatran without coagulation monitoring compared with well-controlled warfarin for prevention of thromboembolism in patients with atrial fibrillation requiring chronic anticoagulant therapy , but the potential for hepatotoxicity requires further investigation OBJECTIVE To determine the minimal clinical ly important difference ( MCID ) of warfarin therapy for the treatment of nonvalvular atrial fibrillation from the perspective of patients using 2 different elicitation methods . DESIGN All patients completed 2 face-to-face interviews , which were 2 weeks apart . For each interview , they were r and omized to receive 1 of 2 elicitation methods : ping-ponging or starting at the known efficacy . SETTING The practice s of 2 university-affiliated family medicine centers ( 8 physicians each ) , 14 community-based family physicians , and 2 cardiologists . PATIENTS Sixty-four patients with nonvalvular atrial fibrillation who were initiated with warfarin therapy at least 3 months before the study . INTERVENTION During each interview , the patients ' MCIDs were determined by using ( 1 ) a pictorial flip chart to describe atrial fibrillation ; the consequences of a minor stroke , a major stroke , and a major bleeding episode ; the chance of stroke if not taking warfarin ; the chance of a major bleeding episode if taking warfarin ; examples of the inconvenience , minor side effects , and costs of warfarin therapy ; and then ( 2 ) 1 of the 2 elicitation methods to determine their MCIDs ( the smallest reduction in stroke risk at which the patients were willing to take warfarin ) . Patients ' knowledge of their stroke risk , acceptability of the interview process , and factors determining their preferences were also assessed . MAIN RESULTS Given a baseline risk of having a stroke in the next 2 years , if not taking warfarin , of 10 of 100 , the mean MCID was 2.01 of 100 ( 95 % confidence interval , 1.60 - 2.42 ) . Fifty-two percent of the patients would take warfarin for an absolute decrease in stroke risk of 1 % over 2 years . Before eliciting their MCIDs , patients showed poor knowledge of their stroke risk , which improved afterward . The interview process was well accepted by the patients . The MCID using the ping-ponging elicitation method was 1.015 of 100 smaller compared with use of the starting at the known efficacy method ( P = .01 ) . CONCLUSIONS We were able to determine the MCID of warfarin therapy for the prevention of stroke from the perspective of patients with nonvalvular atrial fibrillation . Their MCIDs were much smaller than those that have been implied by some experts and clinicians . The interview process , using the flip chart approach , appeared to improve the patients ' knowledge of their disease and its consequences and treatment . The method used to elicit the patients ' MCIDs can have a clinical ly important effect on patient responses . The method used in our study can be generalized to other conditions and , thus , could be helpful in 3 ways : ( 1 ) from a clinical decision-making perspective , it could facilitate patient-physician communication ; ( 2 ) it could clarify the patient perspective when interpreting the results of previously completed trials ; and ( 3 ) it could be used to derive more clinical ly relevant sample sizes for r and omized treatment trials OBJECTIVE To identify echocardiographic predictors of arterial thromboembolism in patients with nonrheumatic atrial fibrillation and to determine whether these add to clinical variables for risk stratification . DESIGN Cohort study of patients assigned to placebo in a r and omized clinical trial . SETTING Five hundred sixty-eight in patients and out patients with nonrheumatic atrial fibrillation assigned to placebo therapy at 15 U.S. medical centers from 1987 to 1989 in the Stroke Prevention in Atrial Fibrillation study . Patients were followed for a mean of 1.3 years . MEASUREMENTS M-mode and two-dimensional ( 2-D ) echocardiograms performed at study entry and interpreted by local cardiologists . The predictive value of 14 echocardiographic variables for later ischemic stroke or systemic embolism was assessed by multivariate analysis . MAIN RESULTS Left ventricular dysfunction from 2-D echocardiograms ( P = 0.003 ) and the size of the left atrium from M-mode echocardiograms ( P = 0.02 ) were the strongest independent predictors of later thromboembolism . Multivariate analysis of these two independent echocardiographic predictors with the three independent clinical predictors of thromboembolism ( history of hypertension , recent congestive heart failure , previous thromboembolism ) identified 26 % of the cohort with a low risk for thromboembolism ( 1.0 % per year ; 95 % Cl , 0.2 % to 4.0 % ) . Compared with risk stratification using clinical variables alone , echocardiographic results altered thromboembolic risk stratification in 18 % of the entire cohort and in 38 % of those without clinical risk factors . CONCLUSIONS Both left ventricular and left atrial variables are significant predictors of thromboembolism in patients with nonvalvular atrial fibrillation . Our results challenge traditional views of the pathogenesis of ischemic stroke in patients with atrial fibrillation and suggest that st and ard echocardiography contributes to risk stratification , differentiating the one third of patients without clinical risk factors who are at increased risk for stroke from the remainder who may not need antithrombotic prophylaxis OBJECTIVES This study examined the influence of left atrial spontaneous echo contrast on the subsequent stroke or embolic event rate and on survival in patients with nonvalvular atrial fibrillation . BACKGROUND Left atrial spontaneous echo contrast is associated with atrial fibrillation and a history of previous stroke or other embolic events . However , the prognostic implication s of spontaneous contrast in patients with nonvalvular atrial fibrillation are unknown . METHOD The study group comprised 272 consecutive patients with nonvalvular atrial fibrillation undergoing transesophageal echocardiography .  Clinical and echocardiographic data were collected at baseline , and patients were prospect ively followed up , and all strokes , other embolic events and deaths were documented . The relation between spontaneous contrast at baseline and subsequent stroke , other embolic events and survival was analyzed . RESULTS Left atrial spontaneous echo contrast was detected at baseline in 161 patients ( 59 % ) . The mean follow-up was 17.5 months . The stroke or other embolic event rate was 12%/year ( 15 strokes , 3 transient ischemic attacks , 2 peripheral embolisms ) in patients with , compared with 3%/year ( 5 strokes ) in patients without , baseline spontaneous contrast ( p = 0.002 ) . In 149 patients without previous thromboembolism , the event rate was 9.5%/year in patients with and 2.2%/year in patients without spontaneous contrast ( p = 0.003 ) . There were 25 deaths in patients with and 11 deaths in patients without spontaneous contrast . Patients with spontaneous contrast had significantly reduced survival ( p = 0.025 ) . On multivariate analysis , spontaneous contrast was the only positive predictor ( odds ratio 3.5 , p = 0.03 ) and warfarin therapy on follow-up the only negative predictor ( odds ratio 0.23 , p = 0.02 ) of subsequent stroke or other embolic events . CONCLUSIONS Transesophageal echocardiography can risk stratify patients with nonvalvular atrial fibrillation by identifying left atrial spontaneous echo contrast . These patients have both a significantly higher risk of developing stroke or other embolic events and a reduced survival , and they may represent a subgroup in whom the risk/benefit ratio of anticoagulation may be most favorable BACKGROUND The Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation ( GLORIA-AF ) was design ed to provide prospect ively collected information on patients with newly diagnosed nonvalvular atrial fibrillation at risk of stroke , with the aim of addressing treatment patterns and questions of effectiveness and safety . METHODS AND RESULTS In this predefined analysis from GLORIA-AF , the baseline characteristics and initial antithrombotic management of the first 10,000 patients in Phase II of this large Registry Program are presented . Overall , 32.3 % of patients received vitamin K antagonists ( VKAs ) and 47.7 % received non-VKA oral anticoagulants ( NOACs ) , while 12.3 % received antiplatelet treatment and 7.6 % did not receive any antithrombotic treatment . Among patients with CHA2DS2-VASc score ≥2 , 6.7 % received no antithrombotic treatment and 10.0 % received aspirin . In Europe , treatment with dabigatran was as common as treatment with VKAs ( 38.8 % and 37.8 % , respectively ) . More than half of the patients were treated with NOACs ( 52.4 % ) , while antiplatelet treatment was given to 5.7 % , and 4.1 % did not receive any antithrombotic treatment . In North America , treatment with dabigatran  ( 25.0 % ) was as common as with VKAs ( 26.1 % ) , but overall NOAC use was more common ( 52.1 % ) than with VKAs ( 26.1 % ) ; however , 14.1 % received antiplatelet treatment , while 7.6 % received no antithrombotic treatment . In Asia , treatment with VKAs ( 31.9 % ) was more prevalent than NOACs ( 25.5 % ) , but antiplatelet treatment was given to 25.8 % , and 16.9 % did not receive any antithrombotic treatment . In Asia , only 60.7 % of patients with high stroke risk received oral anticoagulants ( OACs ) . Paroxysmal atrial fibrillation and minimally symptomatic ( or asymptomatic ) patients were often undertreated with OACs . CONCLUSION In this analysis , OAC use was high in Europe and North America , with overall NOAC use higher than VKA use . A considerable percentage of high-risk patients in North America still received antiplatelet treatment or were untreated , while Asian patients had a high proportion of aspirin use and nontreatment Background Decision aids are often advocated as a means to assist patient and health care provider decision making when faced with complicated treatment or screening decisions . Despite an exponential growth in the availability of decision aids in recent years , their impact on long-term treatment decisions and patient adherence is uncertain due to a paucity of rigorous studies . The choice of antithrombotic therapy for nonvalvular atrial fibrillation ( NVAF ) is one condition for which a trade-off exists between the potential risks and benefits of competing therapies , and the need to involve patients in decision making has been clearly identified . This study will evaluate whether an evidence -based patient decision aid for patients with NVAF can improve the appropriateness of antithrombotic therapy use by patients and their family physicians . Design A multi-center , two-armed cluster r and omized trial based in community family practice s in which patients with NVAF will be r and omized to decision aid or usual care . Patients will receive one of four decision aids depending on their baseline stroke risk . The primary outcome is the provision of " appropriate antithrombotic therapy " at 3 months to study participants ( appropriateness defined as per the 2001 American College of Chest Physicians recommendations for NVAF ) . In addition , the impact of this decision aid on patient knowledge , decisional conflict , well-being , and adherence will be assessed after 3 months , 6 months , and 12 months Background and Purpose — Warfarin is the most effective stroke prevention medication for high-risk individuals with atrial fibrillation , yet it is often underused . This study examined the magnitude of this problem in a large contemporary , prospect i ve stroke registry . Methods — We analyzed data from the Registry of the Canadian Stroke Network , a prospect i ve data base of consecutive patients with stroke admitted to 12 design ated stroke centers in Ontario ( 2003 to 2007 ) . We included patients admitted with an acute ischemic stroke who ( 1 ) had a known history of atrial fibrillation ; ( 2 ) were classified as high risk for systemic emboli according to published guidelines ; and ( 3 ) had no known contraindications to anticoagulation . Primary end points were the use of prestroke antithrombotic medications and admission international normalized ratio . Results — Among patients admitted with a first ischemic stroke who had known atrial fibrillation ( n=597 )  , strokes were disabling in 60 % and fatal in 20 % . Preadmission medications were warfarin ( 40 % ) , antiplatelet therapy ( 30 % ) , and no antithrombotics ( 29 % ) . Of those taking warfarin , three fourths had a subtherapeutic international normalized ratio ( < 2.0 ) at the time of stroke admission . Overall , only 10 % of patients with acute stroke with known atrial fibrillation were therapeutically anticoagulated ( international normalized ratio ≥2.0 ) at admission . In stroke patients with a history of atrial fibrillation and a previous transient ischemic attack or ischemic stroke ( n=323 ) , only 18 % were taking warfarin with therapeutic international normalized ratio at the time of admission for stroke , 39 % were taking warfarin with subtherapeutic international normalized ratio , and 15 % were on no antithrombotic therapy . Conclusions — In high-risk patients with atrial fibrillation admitted with a stroke , and who were c and i date s for anticoagulation , most were either not taking warfarin or were subtherapeutic at the time of ischemic stroke . Many were on no antithrombotic therapy . These findings should encourage greater efforts to prescribe and monitor appropriate antithrombotic therapy to prevent stroke in individuals with atrial fibrillation Abstract Objective : To determine and compare physicians ' and patients ' thresholds for how much reduction in risk of stroke is necessary and how much risk of excess bleeding is acceptable with antithrombotic treatment in people with atrial fibrillation . Design : Prospect i ve observational study . Setting : Tertiary and peripheral referral centres in Nova Scotia , Canada . Participants : 63 physicians who were treating patients with atrial fibrillation and 61 patients at high risk for atrial fibrillation . Main outcome measures : Participants underwent a face to face interview with a probability trade-off tool .  Thresholds were determined for the minimum reduction in risk of stroke necessary and the maximum increase in risk of excess bleeding acceptable for treatment with aspirin and warfarin in people with atrial fibrillation . Results : The minimum number of strokes that needed to be prevented in 100 patients over two years for warfarin to be justified was significantly lower for patients than for physicians ( 1.8 ( SD 1.9 ) v 2.5 ( 1.6 ) , P=0.009 ) , whereas for aspirin there was no difference between patients and physicians ( 1.3 ( 1.3 ) v 1.6 ( 1.5 ) , P=0.29 ) . The maximum number of excess bleeds acceptable in 100 patients over two years for use of warfarin and aspirin was significantly higher for patients than for physicians ( warfarin 17.4 ( 7.1 ) v 10.3 ( 6.1 ) ; aspirin 14.7 ( 8.5 ) v 6.7 ( 6.2 ) ; P<0.001 for both comparisons ) . Conclusions : Patients at high risk for atrial fibrillation placed more value on the avoidance of stroke and less value on the avoidance of bleeding than did physicians who treat patients with atrial fibrillation . The views of the individual patient should be considered when decisions are being made about antithrombotic treatment for people with atrial fibrillation . What is already known on this topic Several observational studies have shown an apparent underuse of antithrombotic drugs in patients with atrial fibrillation , despite evidence of efficacy What this study adds There is considerable variability between physicians and patients in their weighing up of the potential outcomes associated with atrial fibrillation and its treatment For anticoagulation treatment to be acceptable patients required less reduction in risk of stroke and were more tolerant of an increase in risk of bleeding than physicians Physicians varied considerably in how much risk of bleeding they thought was acceptable for a given reduction in risk of stroke associated with antithrombotic BACKGROUND [ corrected ] Atrial fibrillation is an important risk factor for ischaemic stroke . Anticoagulation treatment with warfarin can substantially reduce the risk of stroke in people with atrial fibrillation but concerns about their side-effects have limited their use in clinical practice . However there has been little population -based research on the comorbidity associated with atrial fibrillation and on the prevalence of potential contraindications to anticoagulantion treatment among these patients . AIM To determine the prevalence of known risk factors for ischaemic stroke and possible contraindications to anticoagulant treatment among patients with atrial fibrillation . METHOD One-year prospect i ve cohort study in 60 general practice s in Engl and and Wales with a total population of 502,493 people . Age and sex specific prevalence rates and relative risks of risk factors for ischaemic stroke and possible contraindications to antithrombotic treatment  were calculated . RESULTS The number of patients who had a diagnosis of atrial fibrillation during the year was 1,414 ( 0.3 % ) patients . The prevalence of other nsk factors for ischaemic stroke in patients with atrial fibrillation increased with age in men , from 48 % ( relative risk [ RR ] = 3.78 , 95 % confidence interval [ 95 % CI ] = 3.23 - 4.41 ) at 45 to 64 years to 64 % ( RR = 2.21 , 95 % CI = 2.00 - 2.44 ) at 75years and over A similar increase of 50 % ( RR = 4.36 , 95 % CI = 3.54 - 5.38 ) to 60 % ( RR = 2.07 , 95 % CI = 1.91 - 2.23 ) was seen in women . The percentage of men with atrial fibrillation with at least one contraindication to antithrombotic treatment was 5 % at 45 to 64 years and 14 % at 75 years and over . Among women with atrial fibrillation , 7 % had a contraindication at 45 to 64 years and 16 % at 75 years and over . The all-ages relative risk of a contraindication was 1.17 ( 95 % CI = 0.92 - 1.48 ) in men and 1.53 ( 95 % CI = 1.28 - 1.83 ) in women . Forty per cent ( 575 ) of patients with atrial fibrillation had at least one risk factor for ischaemic stroke and no contraindications to antithrombotic treatment . CONCLUSION Atrial fibrillation is associated with a substantial increase in the prevalence of risk factors for ischaemic stroke . By contrast , potential contraindications for antithrombotic treatment are more evenly distributed among patients with and without atrial fibrillation . Around 40 % of patients with atrial fibrillation in primary care are at high risk of stroke and have no contraindicationsfor antithrombotic treatment 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 The risk for ischemic stroke in patients with atrial fibrillation is related to underlying structural heart disease [ 1 - 3 ] . Although most strokes are believed to arise from embolism of left atrial thrombi [ 4 , 5 ] , other mechanisms may contribute . Transesophageal echocardiography ( TEE ) provides a unique diagnostic window for evaluating the left atrium , left atrial appendage , and thoracic aorta , but the manner in which specific TEE findings in patients with atrial fibrillation correlate with thromboembolic risk and response to therapy has not been fully established [ 6 - 13 ] . We performed TEE in patients with nonvalvular atrial fibrillation who were at high intrinsic risk for thromboembolism and were participating in the Stroke Prevention in Atrial Fibrillation ( SPAF-III ) study , a r and omized clinical trial . In that study , adjusted-dose warfarin ( target international normalized ratio [ INR ] , 2 to 3 ) was compared with combination therapy consisting of low-intensity warfarin ( INR , 1.2 to 1.5 ) plus aspirin , 325 mg/d . The trial was stopped after an interim analysis indicated that the efficacy of adjusted-dose warfarin therapy was superior to that of combination therapy . Low anticoagulation intensity in the combination therapy group yielded high stroke rates that were similar to those expected during treatment with aspirin alone [ 14 , 15 ] . In the current analysis , we 1 ) correlate TEE observations among patients with atrial fibrillation at high risk for thromboembolism with rate of subsequent stroke and 2 ) compare treatment responses . Methods Patients Patients were recruited from the SPAF-III multicenter trial , which was design ed to compare two antithrombotic medication regimens for prevention of ischemic stroke and systemic embolism ( primary events ) . The study , whose design is described else-where in detail [ 14 ] , involved patients with nonvalvular atrial fibrillation who were stratified for risk on the basis of clinical and transthoracic echocardiographic criteria derived from previous analyses [ 15 ] . Women older than 75 years of age and patients of any age and either sex with systolic hypertension ( systolic blood pressure > 160 mm Hg ) , previous thromboembolism , or impaired left ventricular function ( M-mode echocardiographic fractional shortening of 0.25 or recent clinical congestive heart failure ) were r and omly assigned to receive adjusted-dose warfarin ( target INR , 2.0 to 3.0 ) or a combination of low-intensity warfarin ( 0.5 to 3.0 mg/d ; dose was initially adjusted to cause deviation of the INR to 1.2 to 1.5 and was then fixed ) and aspirin . Seventy-three percent of the patients were receiving warfarin at various dose intensities before trial entry ; these patients were equally distributed between assigned treatment groups . Antithrombotic treatment was assigned before performance of TEE and was not influenced by TEE findings . Patients were followed monthly by telephone and in clinic every 3 months , and a st and ard question naire on stroke symptoms was administered annually . All patients whose responses to the question naire suggested the occurrence of stroke were referred for clinical examination by a local affiliated neurologist who was blinded to treatment , and all events were adjudicated by a blinded event verification committee [ 14 ] . This project was design ed to supplement the SPAF-III clinical trial on the basis of the hypothesis that spontaneous echocardiographic contrast detected by TEE identifies patients at high risk for thromboembolism for whom adjusted-dose warfarin  would prove superior to  combination therapy . All participants in the parent study were encouraged , but not required , to provide separate , written informed consent for TEE after r and om assignment to antithrombotic treatment . This was done to prevent the results of TEE from influencing recruitment of patients into the trial or from altering treatment . The intended sample size of 412 TEE examinations was selected to detect an absolute difference in event rates of 3.9 % per year ( based on projected event rates of 5.4 % per year in patients with spontaneous echocardiographic contrast and 1.5 % per year in patients without contrast ) over a mean observation period of 2.5 years . Secondary objectives were to correlate clinical thromboembolic events with function of the left atrial appendage , thrombus of the left atrium and left atrial appendage , and atherosclerotic lesions in the thoracic aorta imaged by TEE . Transesophageal Echocardiography Transesophageal echocardiography was performed within 3 months of enrollment with patients under light sedation and topical anesthesia , according to specific protocol s for acquisition and interpretation [ 16 ] . Commercially available ultrasonography equipment incorporated biplane or multiplane transducers with at least 48 crystals operating at a st and ard frequency of 5 MHz with gray-scale imaging . Signal processing , log compression , and persistence values were established for each manufacturer . Images were interpreted locally , and data were entered into st and ardized forms by echocardiographers who were blinded to antithrombotic treatment assignment but not to patient demographic or clinical features . Original videotaped recordings were collected in a central echocardiographic registry for validation and quality control . To assure generalizability of the results to laboratories used in clinical practice , the analyses reported here are based on image interpretation at the local laboratories . The following features were specifically assessed : left atrial appendage size , peak ante grade ( emptying ) velocity of blood flow in the left atrial appendage , spontaneous echocardiographic contrast in the left atrium or left atrial appendage , thrombus of the left atrium or left atrial appendage , and atherosclerotic disease of the thoracic aorta . Spontaneous echocardiographic contrast was defined as a pattern of slowly swirling intracavitary echodensities imaged with gain setting s adjusted to distinguish background noise . Contrast was classified as faint when visualized intermittently during the cardiac cycle or when enhanced gain setting s were required for detection and was classified as dense when continuously present at st and ard gain . Aortic plaque was classified by location and as either simple or complex according to mobility , ulceration , pedunculation , or thickness greater than 4 mm [ 16 ] . We postulated that reduced emptying velocity from the left atrial appendage , which reflects stasis , would be associated with dense spontaneous echocardiographic contrast and thrombus formation , whereas complex aortic plaque would be a consequence of atherosclerotic vascular abnormality . We also postulated that these findings would predispose patients to ischemic stroke through separate pathogenic mechanisms . Statistical Analysis The analyses reported here were limited to variables accessible only by TEE and were hypothesized a priori to have potential predictive relations to clinical thromboembolism . Baseline comparisons between groups were done by using the chi-square test for categorical data and the Student t-test for continuous variables . The Cox proportional-hazards regression model was used to estimate the univariate relative risk associated with TEE characteristics . The primary analysis compared rates of cerebral ischemic events and systemic embolism among patients who had dense spontaneous echocardiographic contrast detected in the left atrium or left atrial appendage with rates in patients who did not have dense contrast ; the log-rank statistic was used to compare the times to events between these groups . Secondary analyses , conducted similarly , compared event rates in groups that were identified by left atrial appendage size , flow velocity , thrombus , and aortic plaque . For these comparisons , the area of the left atrial appendage was dichotomized at the upper quartile ; flow velocity was dichotomized at the lower quartile . When interaction was seen between treatment and TEE characteristics , analysis of the relation of TEE findings to events was confined to the combination therapy group and treatment effect was described separately ; when no interaction was seen , the analysis was stratified by therapy . The relative reduction in event rate associated with adjusted-dose warfarin therapy was computed as the difference between unity and the rate ratio determined by a Poisson regression model [ 17 ] . A Cox proportional-hazards regression model was fit to confirm the independence of TEE characteristics identified as univariate thromboembolic risk factors . Confidence intervals for event rates were calculated by using a Poisson regression model ; tests of significance were two-sided and were not adjusted for multiple comparisons . All analyses were done according to the intention-to-treat principle . Results Of 1044 high-risk patients with atrial fibrillation enrolled in the r and omized trial , 382 ( 37 % ) volunteered for TEE ( range , 10 % to 80 % of SPAF-III participants recruited at 18 clinical centers offering TEE ) . Salient features of these 382 patients were similar to those of the 662 participants who did not undergo transesophageal imaging ( Table 1 ) . The mean patient age was 71 years , 36 % of patients had clinical ischemic heart disease , and almost half had a history of congestive heart failure . Balanced proportions of patients were assigned to therapy with adjusted-dose warfarin ( n = 190 ) or fixed-dose warfarin and aspirin ( n = 192 ) . Time from r and om assignment of treatment to TEE was similar in the two groups ( mean , 23 days ) . The trial was stopped after a mean observation period of 1.1 years because an interim analysis indicated the lack of efficacy of the combination regimen [ 18 ] . Up to that point , 23 primary events ( all of which were ischemic strokes ) occurred in the subset of participants who had undergone TEE ( event rate , 3.1 % per year in patients assigned to adjusted-dose warfarin compared with 7.8 % per year in those assigned to combination therapy ; P = 0.04 ) . Objectives To determine the accuracy of CHADS2 and CHA2DS2-VASc tools for predicting ischaemic stroke or transient ischaemic attack ( TIA ) and death in patients without a history of atrial fibrillation or flutter ( AF ) . Methods The study included 20 970 patients without known AF enrolled in the Alberta Provincial Project for Outcomes Assessment in Coronary Heart disease ( APPROACH ) prospect i ve registry who were discharged after an acute coronary syndrome ( ACS ) between 2005 and 2011 . The outcome measures were incident ischaemic stroke , TIA or death from any cause . Results Over a median follow-up of 4.1 years , 453 patients ( 2.2 % ) had a stroke ( n=297 ) or TIA ( n=156 ) and 1903 ( 9.0 % ) died . The incidence of stroke or TIA increased with increases in each risk score ( p<0.001 ) , with an absolute annual incidence ≥1 % with CHADS2 ≥3 or CHA2DS2-VASc ≥4 . Both CHADS2 and CHA2DS2-VASc scores had acceptable discrimination performance ( C-statistic=0.68 and 0.71 , respectively ) . The mortality rate was also greater in patients with higher CHADS2 and CHA2DS2-VASc scores ( p<0.0001 ) . Conclusions In patients with ACS but no AF , the CHADS2 and CHA2DS2-VASc scores predict ischaemic stroke/TIA events with similar accuracy to that observed in historical population s with non-valvular AF , but with lower absolute event rates . Further study of the utility of the CHADS2 and CHA2DS2-VASc scores for the assessment of thromboembolic risk and selection of antithrombotic therapy in patients without AF is warranted Background — Many patients with atrial fibrillation are at high risk for stroke and require antithrombotic therapy . Antiarrhythmic drugs have not previously been shown to reduce the risk of stroke in atrial fibrillation . The effect of dronedarone , a new multichannel-blocking antiarrhythmic drug , on stroke has been evaluated in a r and omized , double-blind clinical trial , ATHENA ( A placebo-controlled , double-blind , parallel-arm Trial to assess the efficacy of dronedarone 400 mg BID for the prevention of cardiovascular Hospitalization or death from any cause in patiENts with Atrial fibrillation/atrial flutter ) . Methods and Results — Patients with persistent or paroxysmal atrial fibrillation and at least 1 risk factor for cardiovascular hospitalization were r and omized to receive dronedarone ( 400 mg BID ) or double-blind matching placebo and followed up for a minimum of 1 year to a common termination at 30 months . All strokes that occurred during the study were included in the present post hoc analysis . There were 4628 patients r and omized to placebo or dronedarone .  The baseline risk factors for stroke were well balanced between the 2 groups , and the baseline mean CHADS2 score was 2 . The baseline use of either oral anticoagulant therapy or antiplatelet agent alone was 60 % . Dronedarone reduced the risk of stroke from 1.8 % per year to 1.2 % per year ( hazard ratio 0.66 , 95 % confidence interval 0.46 to 0.96 , P=0.027 ) . The effect of  dronedarone  was similar whether or not patients were receiving oral anticoagulant therapy , and there was a significantly greater effect of  dronedarone  in patients with higher CHADS2 scores . Conclusions — In this post hoc analysis , a reduction in stroke was observed in patients with atrial fibrillation who were receiving usual care , which included antithrombotic therapy and heart rate control , who were r and omized to dronedarone . Further studies to investigate the effect of dronedarone and other antiarrhythmic agents on stroke are indicated Background and Purpose — People with type 2 diabetes are at elevated risk of stroke compared with those without diabetes . Relative risks have been examined in earlier work , but there is no readily available method for predicting the absolute risk of stroke in a diabetic individual . We developed mathematical models to estimate the risk of a first stroke using data from 4549 newly diagnosed type 2 diabetic patients enrolled in the UK Prospect i ve Diabetes Study . Methods — During 30 700 person-years of follow-up , 188 first strokes ( 52 fatal ) occurred . Model fitting was carried out by maximum likelihood estimation using the Newton-Raphson method . Diagnostic plots were used to compare survival probabilities calculated by the model with those calculated using nonparametric methods . Results — Variables included in the final model were duration of diabetes , age , sex , smoking , systolic blood pressure , total cholesterol to high-density lipoprotein cholesterol ratio and presence of atrial fibrillation . Not included in the model were body mass index , hemoglobin A1c , ethnicity , and ex-smoking status . The use of the model is illustrated with a hypothetical study power calculation . Conclusions — This model forecasts the absolute risk of a first stroke in people with type 2 diabetes using variables readily available in routine clinical practice
Female sex was inconsistently associated with stroke risk , whereas the evidence was inconclusive that either heart failure or coronary artery disease is independently predictive of stroke .
Conclusions : Four clinical features ( prior stroke/TIA , advancing age , hypertension , diabetes ) are consistent independent risk factors for stroke in atrial fibrillation patients .
Background : Absolute stroke rates vary widely among patients with nonvalvular atrial fibrillation .
To balance the benefits and risks of chronic antithrombotic prophylaxis , it is important to estimate the absolute risk of stroke for individual patients .